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 Description

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.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Primary Peritoneal Cancer	Drug: Pemetrexed - Phase 1; Drug: Carboplatin - Phase 1; Drug: Pemetrexed - Phase 2; Drug: Carboplatin - Phase 2	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 86 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 and 2 Clinical Trial of ALIMTA® (Pemetrexed) in Combination With Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer
• Study Start Date: July 2005
• Actual Primary Completion Date: February 2010
• Actual Study Completion Date: February 2010

Arms and Interventions

Arm	Intervention/treatment
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.	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)
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.	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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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

Secondary Outcome Measures :

1. 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.

2. 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.
3. 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.
4. 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).
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Argentina

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Bahia Blanca, Argentina, B8000HXM

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Buenos Aires, Argentina, C1199ACK

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Ramos Mejia, Argentina, B1704ESN

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Salta, Argentina, 4400

Canada, Alberta

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Calgary, Alberta, Canada, T2N 4N2

Canada, Ontario

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Toronto, Ontario, Canada, M5G 2M9

Germany

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Berlin, Germany, 13353

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Bonn, Germany, 53127

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Chemnitz, Germany, D-09116

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Duesseldorf, Germany, 40489

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Erlangen, Germany, D-91054

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Essen, Germany, DE-45145

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Hamburg, Germany, 22081

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Jena, Germany, D-07743

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Kiel, Germany, D-24105

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Mainz, Germany, 55131

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Tübingen, Germany, 72076

Poland

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Gdansk, Poland, 80-402

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Olsztyn, Poland, 10-228

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Warsaw, Poland, 00909

Sweden

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Göteborg, Sweden, 416 85

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Lund, Sweden, 22241

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• 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

More Information

Additional Information:

Lilly Clinical Trial Registry 

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
• Other Study ID Numbers: 9516; H3E-MC-JMHH ( Other Identifier: Eli Lilly and Company )
• First Posted: June 21, 2007
• Results First Posted: June 16, 2011
• Last Update Posted: June 16, 2011
• Last Verified: May 2011

Additional relevant MeSH terms:

Peritoneal Neoplasms; Neoplasms by Site; Neoplasms; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Carboplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors