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

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00489359
First received: June 19, 2007
Last updated: May 17, 2011
Last verified: May 2011
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Phase 1 - Maximum Tolerated Dose (MTD) of Pemetrexed in Combination With Carboplatin [ Time Frame: First treatment to toxicity (up to 18 months) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]

    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:
  • Phase 1 - Number of Dose-Limiting Toxicities (DLTs) [ Time Frame: baseline through end of Phase 1 (up to 18 months) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 86
Study Start Date: July 2005
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489359

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:
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00489359     History of Changes
Other Study ID Numbers: 9516, H3E-MC-JMHH
Study First Received: June 19, 2007
Results First Received: February 17, 2011
Last Updated: May 17, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Pemetrexed
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 22, 2014