Trial of Pemetrexed and Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer

• ClinicalTrials.gov Identifier: NCT00489359
• Recruitment Status: Completed
• First Posted: June 21, 2007
• Results First Posted: June 16, 2011
• Last Update Posted: June 16, 2011
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Ovarian Cancer; Primary Peritoneal Cancer
• Interventions: Drug: Pemetrexed - Phase 1; Drug: Carboplatin - Phase 1; Drug: Pemetrexed - Phase 2; Drug: Carboplatin - Phase 2
• Enrollment: 86

Participant Flow

Recruitment Details
Pre-assignment Details	Phase 1 and Phase 2 were conducted in different participants (i.e., Phase 1 participants did not also participate in Phase 2).

Arm/Group Title	Pemetrexed/Carboplatin Phase 1	Pemetrexed/Carboplatin Phase 2
Arm/Group Description	Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin [area under the concentration-time curve (AUC) 5 or 6 mg/mL*min] was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level.	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Period Title: Overall Study
Started	20	66
Completed	13 [1]	37 [1]
Not Completed	7	29
Reason Not Completed
Death	0	2
Progressive Disease	5	6
Lost to Follow-up	1	0
Withdrawal by Subject	1	5
Adverse Event	0	16
[1] Received at least 6 cycles of therapy. Not completed implies participant received <6 cycles.

Baseline Characteristics

Arm/Group Title		Pemetrexed/Carboplatin Phase 1	Pemetrexed/Carboplatin Phase 2	Total
Arm/Group Description		Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin [area under the concentration-time curve (AUC) 5 or 6 mg/mL*min] was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level.	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.	Total of all reporting groups
Overall Number of Baseline Participants		20	66	86
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	20 participants	66 participants	86 participants
		56.99 (11.06)	57.71 (10.44)	57.54 (10.52)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	20 participants	66 participants	86 participants
	Female	20 100.0%	66 100.0%	86 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	20 participants	66 participants	86 participants
Caucasian		20	59	79
Hispanic		0	7	7
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	20 participants	66 participants	86 participants
Canada		0	7	7
Argentina		0	14	14
Poland		0	5	5
Germany		20	31	51
Sweden		0	9	9
Performance Status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	20 participants	66 participants	86 participants
ECOG Status 0		3	46	49
ECOG Status 1		17	20	37
		[1] Measure Description: The Eastern Cooperative Oncology Group (ECOG) score is an overall assessment of the functional/physical performance of the patient. Scores are: 0=Fully active, able to carry on all pre-disease performance without restriction. 1=Restricted in strenuous activity but ambulatory and able to carry out work of a sedentary nature. 2=Ambulatory and capable of self care but unable to carry out any work activities: up and about more than 50% of time. 3=Capable of only limited self care, confined to bed or chair more than 50% of waking hours. 4=Completely disabled, cannot carry on any self care.
Tumor Type; Measure Type: Number; Unit of measure: Participants	Number Analyzed	20 participants	66 participants	86 participants
Ovarian Cancer		15	61	76
Peritoneal Cancer		5	5	10
Platinum-free interval [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	20 participants	66 participants	86 participants
<6 months		0	3	3
6-12 months		6	23	29
>12 months		14	40	54
		[1] Measure Description: The time elapsed since completing platinum-based therapy.

Outcome Measures

1. Primary Outcome

Title	Phase 1 - Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Carboplatin
Description	MTD was to be determined by increasing doses of pemetrexed up to 900 mg/m^2 and carboplatin Area Under the Concentration-Time Curve (AUC) up to 6 mg/mL*min based on observed pattern of dose limiting toxicity (DLT). See Outcome #3 for DLT. If none of 3 initial participants at a given level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level. If at least 2 participants experienced a DLT in Cycle 1 at a dose level, that dose level was considered the MTD. However, based on results from a different Phase 2 Study (NCT00109096), further dose escalations were not explored.
Time Frame	First treatment to toxicity (up to 18 months)

Outcome Measure Data

Analysis Population Description

MTD was not determined in this study, so zero participants were analyzed.

Arm/Group Title	Pemetrexed/Carboplatin Phase 1
Arm/Group Description:	Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

2. Primary Outcome

Title	Phase 2 - Percentage of Participants With Overall Tumor Response (Response Rate)
Description	Response is defined as CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. Response rate (%) = (number of patients with CR+PR/number of patients in Phase 2)*100
Time Frame	baseline to measured progressive disease (PD) (up to 18 months)

Outcome Measure Data

Analysis Population Description

Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements:

Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST.

Arm/Group Title	Pemetrexed/Carboplatin Phase 2
Arm/Group Description:	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Overall Number of Participants Analyzed	61
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	32.8; (21.3 to 46.0)

3. Secondary Outcome

Title	Phase 1 - Number of Dose-Limiting Toxicities (DLTs)
Description	The following toxicities were considered DLT: CTCAE Grade 4 neutropenia (absolute neutrophil count [ANC] <0.5 × 10^9/L lasting ≥7 days. Febrile neutropenia (ANC <1.0 × 10^9/L, fever 38.5°C, and no documented infection). CTCAE Grade 4 thrombocytopenia (platelets <25.0 × 10^9/L). Any hemorrhage with CTCAE Grade ≥3 thrombocytopenia (50.0 × 10^9/L). CTCAE Grade ≥3 nonhematologic toxicity (excluding nausea, vomiting, or CTCAE Grade 3 alanine transaminase (ALT) or aspartate aminotransferase (AST) that returned to baseline prior to next treatment). Treatment delay more than 1 week due to toxicity.
Time Frame	baseline through end of Phase 1 (up to 18 months)

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population).

Arm/Group Title	Pemetrexed/Carboplatin Phase 1
Arm/Group Description:	Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level.
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: DLT events
Number of DLT Events	1
DLT Event: Grade 4 Neutropenia	1

4. Secondary Outcome

Title	Phase 1 - Number of Participants With Adverse Events (Toxicity)
Description	A listing of adverse events is located in the Reported Adverse Event module.
Time Frame	baseline measured to progressive disease (up to 18 months)

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population).

Arm/Group Title	Pemetrexed/Carboplatin Phase 1
Arm/Group Description:	Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level.
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: Participants
Serious Adverse Events	2
Other Adverse Events	19

5. Secondary Outcome

Title	Phase 1 - Recommended Dose of Pemetrexed for Phase 2
Description	MTD was to be used as Phase 2 recommended dose. MTD was to be determined by increasing doses of pemetrexed up to 900 mg/m^2 based on observed pattern of dose limiting toxicity (DLT: See Outcome #3). If none of 3 initial participants at a given level had a DLT in Cycle 1, enrollment proceeded to next dose level. If at least 2 participants had a DLT in Cycle 1 at a dose level, that dose level was considered the MTD. However, based on results from another Phase 2 Study (NCT00109096), further dose escalations were not explored and dose was selected based on results of that Phase 2 Study.
Time Frame	baseline measured to progressive disease (up to 18 months)

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population).

Arm/Group Title	Pemetrexed/Carboplatin Phase 1
Arm/Group Description:	Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level.
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: mg/m^2 (milligrams per square meter)
	500

6. Secondary Outcome

Title	Phase 1 - Recommended Area Under the Curve (AUC) Dose of Carboplatin for Phase 2
Description	MTD was to be used as Phase 2 recommended dose. MTD determined by increasing doses up to AUC 6 mg/mL*min based on pattern of DLT (Outcome #3). If none of 3 initial participants at given level had DLT in Cycle 1, enrollment proceeded to next dose level. If at least 2 participants had DLT in Cycle 1 at dose level, that dose level was considered MTD. However, based on results from Phase 2 Study (NCT00109096), further dose escalations were not explored: carboplatin dose was selected based on standard dose employed in control arm of first-line therapy for epithelial ovarian cancer (Bookman 2006).
Time Frame	baseline measured to progressive disease (up to 18 months)

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population).

Arm/Group Title	Pemetrexed/Carboplatin Phase 1
Arm/Group Description:	Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level.
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: mg/mL*min
	6

7. Secondary Outcome

Title	Phase 1 - Number of Participants With Tumor Response
Description	Patients were analyzed by Cancer Antigen-125 (CA-125) response criteria and RECIST guidelines. Possible evaluations include: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame	baseline measured to progressive disease (up to 18 months)

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population).

Arm/Group Title	Pemetrexed/Carboplatin Phase 1
Arm/Group Description:	Pemetrexed (500, 600, 700, 800, or 900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5 or AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion. Participant accrual and dose escalations were dependent upon the observed pattern of dose limiting toxicity (DLT). If none of the 3 initial participants of a given dose level experienced a DLT in Cycle 1, enrollment proceeded to the next dose level.
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: Participants
Complete Response (CR)	12
Partial Response (PR)	4
Stable Disease (SD)	1
Progressive Disease (PD)	2

8. Secondary Outcome

Title	Phase 2 - Time to Response (TTR)
Description	Response is defined as CR (Complete Response) or PR (Partial Response) per RECIST criteria. Possible evaluations include: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame	First treatment to response (up to 31 months)

Outcome Measure Data

Analysis Population Description

Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements:

Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST.

Arm/Group Title	Pemetrexed/Carboplatin Phase 2
Arm/Group Description:	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Overall Number of Participants Analyzed	20
Median (95% Confidence Interval); Unit of Measure: Months
	1.8; (1.4 to 2.8)

9. Secondary Outcome

Title	Phase 2 - Duration of Response (DOR)
Description	Duration of response is defined as the time from first observation of Complete Response or Partial Response to the first observation of Progressive Disease or death from any cause. For patients who are still alive at the time of analysis, and who do not have Progressive Disease, duration of response will be censored at the date of the last objective progression-free disease assessment.
Time Frame	time of response to progressive disease (up to 31 months)

Outcome Measure Data

Analysis Population Description

Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements:

Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST.

Arm/Group Title	Pemetrexed/Carboplatin Phase 2
Arm/Group Description:	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Overall Number of Participants Analyzed	20
Median (95% Confidence Interval); Unit of Measure: Months
	9.1; (6.9 to 10.2)

10. Secondary Outcome

Title	Phase 2 - Time to Disease Progression
Description	Time to objective progressive disease (TTPD) is defined as the time from the date of study enrollment to the date of objectively determined Progressive Disease (PD). For patients who die without objective PD (including death from study disease), TTPD will be censored at the date of the last objective progression-free disease assessment. For patients who are still alive at the time of analysis, and who do not have PD, TTPD will be censored at the date of the last objective progression-free disease assessment.
Time Frame	baseline to measured progressive disease (up to 31 months)

Outcome Measure Data

Analysis Population Description

Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements:

Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined using RECIST.

Arm/Group Title	Pemetrexed/Carboplatin Phase 2
Arm/Group Description:	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Overall Number of Participants Analyzed	61
Median (95% Confidence Interval); Unit of Measure: Months
	9.5; (8.3 to 11.3)

11. Secondary Outcome

Title	Phase 2 - Time to Treatment Failure
Description	Time to treatment failure (TTTF) is defined as the time from the date of study enrollment to the date of the first observation of disease progression, death from any cause, or early discontinuation of treatment (any reason). For patients who are alive, progression-free, and have not discontinued early at the time of analysis, TTTF will be censored at the date of the last objective progression-free disease assessment.
Time Frame	First treatment to discontinuation of study drug, progressive disease, or death (up to 31 months)

Outcome Measure Data

Analysis Population Description

Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements:

Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST.

Arm/Group Title	Pemetrexed/Carboplatin Phase 2
Arm/Group Description:	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Overall Number of Participants Analyzed	61
Median (95% Confidence Interval); Unit of Measure: Months
	7.1; (4.6 to 8.5)

12. Secondary Outcome

Title	Phase 2 - Overall Survival
Description	Overall survival is defined as the time from the date of study enrollment to the date of death from any cause. This analysis was not done due to the high number of censored patients.
Time Frame	baseline to date of death from any cause (up to 31 months)

Outcome Measure Data

Analysis Population Description

Protocol Qualified (PQ) population. This analysis was not done due to the high number of censored patients.

Arm/Group Title	Pemetrexed/Carboplatin Phase 2
Arm/Group Description:	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

13. Secondary Outcome

Title	Phase 2 - Number of Participants With Adverse Events (Toxicity)
Description	A listing of adverse events is located in the Reported Adverse Event module.
Time Frame	baseline through end of Phase 2 (up to 31 months)

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) population - all patients that consented and were successfully screened (note patient may or may not have received treatment; patients that were screen failures were not included in this population).

Arm/Group Title	Pemetrexed/Carboplatin Phase 2
Arm/Group Description:	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Overall Number of Participants Analyzed	66
Measure Type: Number; Unit of Measure: participants
Serious Adverse Events	15
Other Adverse Events	63

14. Secondary Outcome

Title	Phase 2 - Progression-Free Survival
Description	Progression-free survival (PFS) is defined as the time from the date of study enrollment to the date of objectively determined PD or death from any cause, whichever comes first. For patients who are still alive at the time of analysis, and who do not have PD, PFS will be censored at the date of the last objective progression-free disease assessment.
Time Frame	baseline to measured progressive disease (up to 31 months)

Outcome Measure Data

Analysis Population Description

Protocol Qualified (PQ) population. This population includes all patients in the Phase 2 study who met the following requirements:

Histologic diagnosis of ovarian or primary peritoneal cancer, no concurrent chemotherapy, treatment with at least 1 dose of pemetrexed or 1 dose of carboplatin, presence of measurable disease as defined by RECIST.

Arm/Group Title	Pemetrexed/Carboplatin Phase 2
Arm/Group Description:	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6 mg/mL*min) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
Overall Number of Participants Analyzed	61
Median (95% Confidence Interval); Unit of Measure: Months
	9.4; (8.3 to 11.1)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Adverse events are reported regardless of potential relatedness to study drug or Grade (severity).
Arm/Group Title	Pemetrexed 500 + Carboplatin AUC 5 (Phase 1)		Pemetrexed 600 + Carboplatin AUC 5 (Phase 1)		Pemetrexed 600 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 700 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 800 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 900 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 500 + Carboplatin AUC 6 (Phase 2)
Arm/Group Description	Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.		Pemetrexed (600 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 5) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.		Pemetrexed (600 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.		Pemetrexed (700 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.		Pemetrexed (800 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.		Pemetrexed (900 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.		Pemetrexed (500 mg/m^2) was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin (AUC 6) was administered intravenously over approximately 30 minutes on Day 1 of a 21-day cycle, beginning approximately 30 minutes after the end of the pemetrexed infusion.
All-Cause Mortality
	Pemetrexed 500 + Carboplatin AUC 5 (Phase 1)		Pemetrexed 600 + Carboplatin AUC 5 (Phase 1)		Pemetrexed 600 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 700 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 800 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 900 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 500 + Carboplatin AUC 6 (Phase 2)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--		--/--		--/--		--/--
Serious Adverse Events
	Pemetrexed 500 + Carboplatin AUC 5 (Phase 1)		Pemetrexed 600 + Carboplatin AUC 5 (Phase 1)		Pemetrexed 600 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 700 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 800 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 900 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 500 + Carboplatin AUC 6 (Phase 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25.00%)		0/3 (0.00%)		0/4 (0.00%)		0/3 (0.00%)		1/3 (33.33%)		1/3 (33.33%)		15/66 (22.73%)
Blood and lymphatic system disorders
Anaemia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	3/66 (4.55%)	5
Pancytopenia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Thrombocytopenia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Cardiac disorders
Tachycardia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Gastrointestinal disorders
Abdominal pain † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Ascites † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Constipation † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/66 (0.00%)	0
Gastrointestinal haemorrhage † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Ileus † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Nausea † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Subileus † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Umbilical hernia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Vomiting † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
General disorders
Multi-organ failure † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Immune system disorders
Drug hypersensitivity † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	3/66 (4.55%)	3
Infections and infestations
Bronchopulmonary aspergillosis † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Herpes zoster † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Sepsis † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Urinary tract infection † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Zygomycosis † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Renal and urinary disorders
Renal failure † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Renal failure acute † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
Pleural effusion † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Pulmonary oedema † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pemetrexed 500 + Carboplatin AUC 5 (Phase 1)		Pemetrexed 600 + Carboplatin AUC 5 (Phase 1)		Pemetrexed 600 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 700 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 800 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 900 + Carboplatin AUC 6 (Phase 1)		Pemetrexed 500 + Carboplatin AUC 6 (Phase 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100.00%)		3/3 (100.00%)		4/4 (100.00%)		3/3 (100.00%)		3/3 (100.00%)		2/3 (66.67%)		63/66 (95.45%)
Blood and lymphatic system disorders
Anaemia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	2/4 (50.00%)	2	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	19/66 (28.79%)	32
Leukopenia † 1	0/4 (0.00%)	0	2/3 (66.67%)	2	2/4 (50.00%)	2	1/3 (33.33%)	2	2/3 (66.67%)	4	0/3 (0.00%)	0	20/66 (30.30%)	65
Neutropenia † 1	0/4 (0.00%)	0	2/3 (66.67%)	4	3/4 (75.00%)	3	1/3 (33.33%)	5	2/3 (66.67%)	3	0/3 (0.00%)	0	32/66 (48.48%)	109
Thrombocytopenia † 1	2/4 (50.00%)	3	1/3 (33.33%)	1	3/4 (75.00%)	5	3/3 (100.00%)	3	2/3 (66.67%)	2	0/3 (0.00%)	0	14/66 (21.21%)	41
Ear and labyrinth disorders
Tinnitus † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
Vertigo † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Eye disorders
Conjunctivitis † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Eye pain † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Keratoconjunctivitis sicca † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	1/4 (25.00%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Lacrimation increased † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	1/4 (25.00%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	10/66 (15.15%)	19
Visual acuity reduced † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	2	0/66 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	2/4 (50.00%)	2	2/3 (66.67%)	7	1/4 (25.00%)	1	1/3 (33.33%)	1	2/3 (66.67%)	3	0/3 (0.00%)	0	9/66 (13.64%)	11
Abdominal pain upper † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	4/66 (6.06%)	4
Cheilitis † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Constipation † 1	4/4 (100.00%)	24	2/3 (66.67%)	12	2/4 (50.00%)	3	3/3 (100.00%)	9	1/3 (33.33%)	1	2/3 (66.67%)	4	21/66 (31.82%)	39
Diarrhoea † 1	0/4 (0.00%)	0	1/3 (33.33%)	2	1/4 (25.00%)	1	1/3 (33.33%)	2	2/3 (66.67%)	5	0/3 (0.00%)	0	10/66 (15.15%)	16
Dry mouth † 1	2/4 (50.00%)	2	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	3
Dyspepsia † 1	2/4 (50.00%)	4	0/3 (0.00%)	0	1/4 (25.00%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	5/66 (7.58%)	6
Flatulence † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Gingivitis † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Nausea † 1	4/4 (100.00%)	15	2/3 (66.67%)	10	3/4 (75.00%)	9	3/3 (100.00%)	12	3/3 (100.00%)	12	2/3 (66.67%)	5	42/66 (63.64%)	108
Salivary hypersecretion † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Stomatitis † 1	3/4 (75.00%)	3	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	2/3 (66.67%)	5	1/3 (33.33%)	1	10/66 (15.15%)	13
Tongue discolouration † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Vomiting † 1	2/4 (50.00%)	2	2/3 (66.67%)	5	4/4 (100.00%)	8	3/3 (100.00%)	13	3/3 (100.00%)	8	1/3 (33.33%)	1	27/66 (40.91%)	45
General disorders
Chills † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	2/4 (50.00%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	2
Face oedema † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Fatigue † 1	3/4 (75.00%)	15	2/3 (66.67%)	2	4/4 (100.00%)	7	2/3 (66.67%)	3	3/3 (100.00%)	5	1/3 (33.33%)	2	33/66 (50.00%)	57
Mucosal inflammation † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	10/66 (15.15%)	18
Oedema peripheral † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	5/66 (7.58%)	8
Pain † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Pyrexia † 1	1/4 (25.00%)	1	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	4/66 (6.06%)	5
Immune system disorders
Drug hypersensitivity † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	17/66 (25.76%)	41
Hypersensitivity † 1	1/4 (25.00%)	1	1/3 (33.33%)	1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	1/3 (33.33%)	1	1/66 (1.52%)	2
Infections and infestations
Cystitis † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	4/66 (6.06%)	4
Influenza † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Nasopharyngitis † 1	2/4 (50.00%)	2	2/3 (66.67%)	2	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	7/66 (10.61%)	7
Investigations
Alanine aminotransferase increased † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	8/66 (12.12%)	11
Aspartate aminotransferase increased † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	6/66 (9.09%)	10
Blood glucose increased † 1	0/4 (0.00%)	0	1/3 (33.33%)	3	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Haemoglobin † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
Haemoglobin decreased † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	18/66 (27.27%)	27
Neutrophil count decreased † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	10/66 (15.15%)	44
Platelet count decreased † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	16/66 (24.24%)	40
White blood cell count decreased † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	4/66 (6.06%)	15
Metabolism and nutrition disorders
Anorexia † 1	0/4 (0.00%)	0	1/3 (33.33%)	2	2/4 (50.00%)	2	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	5/66 (7.58%)	8
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	2/4 (50.00%)	4	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Back pain † 1	3/4 (75.00%)	3	0/3 (0.00%)	0	2/4 (50.00%)	3	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	2/66 (3.03%)	2
Bone pain † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Joint swelling † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/66 (0.00%)	0
Musculoskeletal pain † 1	1/4 (25.00%)	1	1/3 (33.33%)	1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Myalgia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
Pain in extremity † 1	0/4 (0.00%)	0	2/3 (66.67%)	3	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
Nervous system disorders
Ageusia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/66 (0.00%)	0
Dizziness † 1	0/4 (0.00%)	0	2/3 (66.67%)	2	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	6/66 (9.09%)	6
Headache † 1	2/4 (50.00%)	4	3/3 (100.00%)	6	3/4 (75.00%)	6	1/3 (33.33%)	1	1/3 (33.33%)	1	2/3 (66.67%)	2	5/66 (7.58%)	10
Neuropathy peripheral † 1	1/4 (25.00%)	3	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Paraesthesia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	2	2/3 (66.67%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Peripheral sensory neuropathy † 1	0/4 (0.00%)	0	2/3 (66.67%)	2	1/4 (25.00%)	2	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	6/66 (9.09%)	7
Polyneuropathy † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Psychiatric disorders
Insomnia † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	4/66 (6.06%)	4
Sleep disorder † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Renal and urinary disorders
Polyuria † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/4 (25.00%)	3	1/3 (33.33%)	1	1/4 (25.00%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	3/66 (4.55%)	3
Dry throat † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/66 (0.00%)	0
Dysphonia † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Dyspnoea † 1	1/4 (25.00%)	2	2/3 (66.67%)	2	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	4/66 (6.06%)	6
Epistaxis † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Nasal mucosal disorder † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/66 (0.00%)	0
Oropharyngeal pain † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	2
Rhinitis allergic † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	3	0/3 (0.00%)	0	0/66 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia † 1	2/4 (50.00%)	2	1/3 (33.33%)	1	0/4 (0.00%)	0	1/3 (33.33%)	1	2/3 (66.67%)	2	0/3 (0.00%)	0	18/66 (27.27%)	19
Dry skin † 1	0/4 (0.00%)	0	2/3 (66.67%)	2	1/4 (25.00%)	1	0/3 (0.00%)	0	1/3 (33.33%)	2	0/3 (0.00%)	0	4/66 (6.06%)	4
Eczema † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Erythema † 1	0/4 (0.00%)	0	1/3 (33.33%)	2	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
Hyperhidrosis † 1	1/4 (25.00%)	3	1/3 (33.33%)	3	2/4 (50.00%)	6	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
Leukoplakia † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Night sweats † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	2/4 (50.00%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Pruritus † 1	1/4 (25.00%)	1	1/3 (33.33%)	1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	6/66 (9.09%)	10
Rash † 1	1/4 (25.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	1/3 (33.33%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	10/66 (15.15%)	13
Scar pain † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Skin hyperpigmentation † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/66 (1.52%)	1
Swelling face † 1	0/4 (0.00%)	0	1/3 (33.33%)	1	1/4 (25.00%)	2	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/66 (0.00%)	0
Vascular disorders
Flushing † 1	1/4 (25.00%)	1	2/3 (66.67%)	5	3/4 (75.00%)	3	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	3	6/66 (9.09%)	12
Hot flush † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	1/3 (33.33%)	1	0/3 (0.00%)	0	0/3 (0.00%)	0	2/66 (3.03%)	2
Lymphoedema † 1	0/4 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/3 (33.33%)	1	0/66 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979

Publications:

Bookman MA. 2006. GOG0182-ICON5: 5-arm phase III randomized trial of paclitaxel (P) and carboplatin (C) vs combinations with gemcitabine (G), PEG-lipososomal doxorubicin (D), or topotecan (T) in patients (pts) with advanced-stage epithelial ovarian (EOC) or primary peritoneal (PPC) carcinoma. J Clin Oncol 24 (suppl 18S). Abstract 5002.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sehouli J, Alvarez AM, Manouchehrpour S, Ghatage P, Szczylik C, Zimmermann A, Bauknecht T, Look KY, Oskay-Öezcelik G. A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer. Gynecol Oncol. 2012 Feb;124(2):205-9. doi: 10.1016/j.ygyno.2011.09.007. Epub 2011 Nov 1.

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00489359 History of Changes
• Other Study ID Numbers: 9516; H3E-MC-JMHH ( Other Identifier: Eli Lilly and Company )
• First Submitted: June 19, 2007
• First Posted: June 21, 2007
• Results First Submitted: February 17, 2011
• Results First Posted: June 16, 2011
• Last Update Posted: June 16, 2011