E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
platinum sensitive recurrent ovarian or primary peritoneal cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033130 |
E.1.2 | Term | Ovarian cancer NOS |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the Phase 1 portion of this study is to determine the MTD of the combination therapy of pemetrexed and carboplatin when administered to patients with platinum-sensitive recurrent ovarian cancer. Subsequent references to the study population (“patients with ovarian cancer”) will include the subpopulation of patients with primary peritoneal cancer.
The primary objective of the Phase 2 portion of this study is to determine the overall tumor response rate of the combination therapy of pemetrexed and carboplatin when administered to patients with platinum-sensitive recurrent ovarian cancer. Subsequent references to the study population (“patients with ovarian cancer”) will include the subpopulation of patients with primary peritoneal cancer. |
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E.2.2 | Secondary objectives of the trial |
Phase 1 : - to determine the dose limiting toxicities (DLT) of the combination therapy of pemetrexed and carboplatin in patients with platinum-sensitive recurrent ovarian cancer - to determine the quantitative and qualitative toxicities of pemetrexed in combination with carboplatin - to determine a recommended dose of the combination therapy of pemetrexed and carboplatin for future Phase 2 studies - to document the antitumor activity of pemetrexed and carboplatin in patients with platinum-sensitive recurrent ovarian cancer through tumor response assessment.
Phase 2: - to determine the following time-to-event parameters o time to response o duration of response o time to objective disease progression o time to treatment failure o objective progression-free survival o overall survival. - to determine the safety and quantitative and qualitative toxicities |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
It was decided in July 2007 not to do the sub-study in H3E-MC-JMHH phase I/II. The decision was based on review of data from another study. No patients in Sweden has enrolled in the sub-study.
Companion Translational Research Protocol H3E-MC-JMHH. 03.Jan.2005, first version of the protocol. Primary Objective: Assess the association between levels of individual molecular markers and overall tumor response following treatment with pemetrexed and carboplatin. Secondary Objectives: impact of tumor markers on: - time-to-event efficacy paramenters (like TTTF, PFS, or overall survival) - the incidence of severe toxicities |
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E.3 | Principal inclusion criteria |
Patients are eligible to be included in the study only if they meet all of the following criteria: [1] histologic diagnosis of ovarian or primary peritoneal cancer that is not amenable to curative therapy. [2] patients must have platinum-sensitive recurrent ovarian cancer. Platinum sensitive ovarian cancer is defined as disease that recurs at least 6 months after completion of prior platinum-based therapy. Best response to prior platinum-based therapy must have been CR, PR, SD, or not evaluable due to optimal debulking surgery. [3] prior radiation therapy is allowed, and patients must have recovered from the acute toxic effects of the treatment prior to study entry, but must have been completed at least 2 weeks prior to study enrollment. Prior radiation therapy must not have involved more than 25% of the bone marrow. [4] patients enrolling in the Phase 1 portion of the protocol may have either measurable or nonmeasurable disease as defined by Response Criteria in Solid Tumors (RECIST) guidelines. (Therasse et al. 2000; refer to Section 6.1.1.3) [5] patients enrolling in the Phase 2 portion of the protocol must have: - measurable disease as defined by the RECIST guidelines, or [6] performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale (Protocol Attachment JMHH.3). [7] estimated life expectancy of at least 24 weeks. [8] patient compliance and geographic proximity that allow adequate follow-up. [9] adequate organ function including the following: - adequate bone marrow reserve: absolute neutrophil count (ANC) ≥1.5 x 10e9/L, platelets ≥100 x 10e9/L, and hemoglobin ≥9 g/dL. - hepatic: bilirubin ≤1.5 times the upper limit of normal (ULN), alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤3.0 times ULN (AP, AST, and ALT ≤5.0 times ULN is acceptable if due to liver metastases). - renal: calculated creatinine clearance (CrCl) ≥45 mL/min based on the standard Cockcroft and Gault formula or on measured GFR using the appropriate radiolabeled method (51-CrEDTA or Tc99m-DTPA). [10] signed informed consent from patient or legal representative is required. [11] women at least 18 years of age. [12] patients with reproductive potential must use a reliable contraceptive method if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) during the study. Patients with reproductive potential must have a negative serum or urine pregnancy test within 7 days of study enrollment. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: [13] more than 2 lines of therapy for ovarian or primary peritoneal cancer. This includes high-dose therapy, consolidation therapy, maintenance therapy, or noncytotoxic targeted agents. Noncytotoxic targeted agents include (but are not limited to) hormonal therapies, monoclonal antibodies, cytokines, small molecule inhibitors of signal transduction, or any other agents with anti-tumor activity. [14] pregnant or breast feeding. [15] serious concomitant systemic disorders (for example, active infection) that, in the opinion of the investigator, would compromise the safety of the patient and her ability to complete the study. [16] 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. [17] inability to interrupt the use of aspirin and/or other nonsteroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents, such as piroxicam). [18] peripheral neuropathy ≥NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 (see CTCAE Investigator Guide, Version 3.0). [19] inability or unwillingness to take folic acid and vitamin B12 supplementation, and corticosteroids. [20] previous completion of or withdrawal from this study or any other study investigating pemetrexed. [21] inability to comply with protocol or study procedures. [22] have a clinically significant third-space fluid (for example, pleural effusion or ascites) that cannot be managed with drainage. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 1: Maximum tolerated dose Phase 2: Overall tumor response rate
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial definition: The sponsor will consider that it has sufficient data to close the study for analyses and reports when at least 70% of enrolled Phase 2 patients have experienced disease progression or have died, or 12 months after the last patient is enrolled, whichever occurs later.
It is reasonable to have a follow-up period after the treatment phase for studies in oncology, since time to event parameters, like time to progression and death, are important. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |