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

Tracking Information
First Submitted Date ICMJE	June 19, 2007
First Posted Date ICMJE	June 21, 2007
Results First Submitted Date	February 17, 2011
Results First Posted Date	June 16, 2011
Last Update Posted Date	June 16, 2011
Study Start Date ICMJE	July 2005
Actual Primary Completion Date	February 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 17, 2011)	Phase 1 - Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Carboplatin [ Time Frame: First treatment to toxicity (up to 18 months) ]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.; Phase 2 - Percentage of Participants With Overall Tumor Response (Response Rate) [ Time Frame: baseline to measured progressive disease (PD) (up to 18 months) ]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
Original Primary Outcome Measures ICMJE; (submitted: June 19, 2007)	Overall tumor response rate
Change History	Complete list of historical versions of study NCT00489359 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 17, 2011)	Phase 1 - Number of Dose-Limiting Toxicities (DLTs) [ Time Frame: baseline through end of Phase 1 (up to 18 months) ]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.; Phase 1 - Number of Participants With Adverse Events (Toxicity) [ Time Frame: baseline measured to progressive disease (up to 18 months) ]A listing of adverse events is located in the Reported Adverse Event module.; Phase 1 - Recommended Dose of Pemetrexed for Phase 2 [ Time Frame: baseline measured to progressive disease (up to 18 months) ]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.; Phase 1 - Recommended Area Under the Curve (AUC) Dose of Carboplatin for Phase 2 [ Time Frame: baseline measured to progressive disease (up to 18 months) ]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).; Phase 1 - Number of Participants With Tumor Response [ Time Frame: baseline measured to progressive disease (up to 18 months) ]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.; Phase 2 - Time to Response (TTR) [ Time Frame: First treatment to response (up to 31 months) ]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.; Phase 2 - Duration of Response (DOR) [ Time Frame: time of response to progressive disease (up to 31 months) ]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.; Phase 2 - Time to Disease Progression [ Time Frame: baseline to measured progressive disease (up to 31 months) ]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.; Phase 2 - Time to Treatment Failure [ Time Frame: First treatment to discontinuation of study drug, progressive disease, or death (up to 31 months) ]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.; Phase 2 - Overall Survival [ Time Frame: baseline to date of death from any cause (up to 31 months) ]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.; Phase 2 - Number of Participants With Adverse Events (Toxicity) [ Time Frame: baseline through end of Phase 2 (up to 31 months) ]A listing of adverse events is located in the Reported Adverse Event module.; Phase 2 - Progression-Free Survival [ Time Frame: baseline to measured progressive disease (up to 31 months) ]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.
Original Secondary Outcome Measures ICMJE; (submitted: June 19, 2007)	To determine safety of the combination therapy.; To determine time to event parameters.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Trial of Pemetrexed and Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer
Official Title ICMJE	A Phase 1 and 2 Clinical Trial of ALIMTA® (Pemetrexed) in Combination With Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer
Brief Summary	The purpose of this study is to determine efficacy of the combination therapy of pemetrexed and carboplatin as treatment for patients with platinum-sensitive ovarian cancer. This study also includes patients with primary peritoneal cancer.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Ovarian Cancer; Primary Peritoneal Cancer
Intervention ICMJE	Drug: Pemetrexed - Phase 1 500, 600, 700, 800, or 900 milligrams per square meter (mg/m^2), administered intravenously (IV), every 21 days x 6 cycles, dose escalate to Maximum Tolerated Dose (MTD) Other Names: LY231514 Alimta; Drug: Carboplatin - Phase 1 area under the concentration time curve (AUC) 5 or 6 mg/mL*min, administered intravenously (IV), every 21 days x 6 cycles, dose escalation to Maximum Tolerated Dose (MTD); Drug: Pemetrexed - Phase 2 Dose determined from Phase 1: 500 mg/m^2, administered IV, every 21 days x 6 cycles Other Names: LY231514 Alimta; Drug: Carboplatin - Phase 2 Dose determined from Phase 1: AUC 6 mg/mL*min, administered IV, every 21 days x 6 cycles
Study Arms	Experimental: Pemetrexed/Carboplatin Phase 1 Pemetrexed was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin 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. Interventions: Drug: Pemetrexed - Phase 1 Drug: Carboplatin - Phase 1; Experimental: Pemetrexed/Carboplatin Phase 2 Pemetrexed was administered intravenously over approximately 10 minutes on Day 1 of a 21-day cycle. Carboplatin 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. Interventions: Drug: Pemetrexed - Phase 2 Drug: Carboplatin - Phase 2
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.; 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 12, 2010)	86
Original Estimated Enrollment ICMJE; (submitted: June 19, 2007)	100
Actual Study Completion Date	February 2010
Actual Primary Completion Date	February 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Diagnosis of ovarian or primary peritoneal cancer confirmed by pathology; Patients must have recurrent ovarian cancer which is sensitive to platinum therapy; Prior radiation therapy is allowed Measurable disease as defined by the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines, or non-measurable but cancer antigen 125 (CA-125) greater than or equal to 2X upper limit. Exclusion Criteria: More than 2 lines of therapy for ovarian or primary peritoneal cancer.; Pregnant or breast feeding.; Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Canada, Germany, Poland, Sweden
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00489359
Other Study ID Numbers ICMJE	9516; H3E-MC-JMHH ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Chief Medical Officer, Eli Lilly
Study Sponsor ICMJE	Eli Lilly and Company
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account	Eli Lilly and Company
Verification Date	May 2011
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP