Second-Line Therapy Study For Potentially Platinum-Sensitive Relapsed Ovarian Cancer

Study Overview
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Brief Summary
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This study was designed to find the most effective and safest doses of both HYCAMTIN and CARBOPLATIN that can be given for the treatment of ovarian cancer. This study may allow researchers to determine the effectiveness of combining HYCAMTIN and CARBOPLATIN.

Official Title
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An Open-Label, Single-Arm, Phase II Study of IV Weekly (Days 1 and 8 Every 21 Days) HYCAMTIN in Combination With Carboplatin (Day 1 Every 21 Days) as Second-Line Therapy in Subjects With Potentially Platinum-Sensitive Relapsed Ovarian Cancer

Conditions
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Ovarian Cancer, Neoplasms, Ovarian

Intervention / Treatment
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* Drug: topotecan
* Drug: CARBOPLATIN


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subject must have baseline laboratory values as follows: Hemoglobin 9.0 g/dL Neutrophils 1,500/mm3 Platelets 100,000/mm3 Creatinine 1.5 mg/dL ( 133 mol/l) or creatinine clearance 60 mL/min Serum bilirubin < 2.0 mg/dL (< 35 umol/L) SGOT/AST, SGPT/ALT and alkaline phosphatase < 2 times ULN if liver metastases are absent by abdominal CT or MRI or < 5 times ULN if liver metastases are present Subject is allowed to have received, but is not required to have received, one additional prior non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction Subject is female 18 years of age with an ECOG Performance Status of 0, 1 or 2 Subject has recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer which was histologically confirmed at the time of the primary diagnosis Subject has received one prior platinum-based chemotherapeutic regimen (containing either carboplatin or cisplatin) for the treatment of primary disease. Consolidation chemotherapy is not permitted Subject's disease is considered potentially platinum-sensitive (i.e., have had a platinum-free interval following complete response to carboplatin or cisplatin of greater than 6 months) Subject must have at least one measurable lesion as determined by diagnostic studies including CT or MRI or physical exam. Measurable disease must be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be 20 mm in their longest dimension when measured by conventional techniques, including palpation, plain X-ray, CT and MRI, or 10 mm when measured by spiral CT. Palpable tumor masses that cannot be evaluated radiologically must have 2 diameters 20 mm. An attempt to document lesion size by ultrasound should be undertaken for palpable lesions not visualized on CT (or MRI). The same diagnostic imaging method used to evaluate disease must be used throughout the study to evaluate lesions consistently Stable blood, liver and renal functions. Subjects of child-bearing potential must be practicing adequate contraception (e.g. oral contraceptives, diaphragm plus spermicide, or IUD) for at least 3 months prior to study start. The same contraceptive method should be used throughout the study and continue for at least 4 weeks after the end of the study Exclusion criteria: Pregnant or lactating. Subject has received more than 1 prior chemotherapy regimen or a history of consolidation cytotoxic chemotherapy Subject has concomitant or history of previous malignancies, with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for 5 years Subject has brain metastases as documented by CT or MRI. Note: Asymptomatic subjects do not require CT or MRI to rule out brain metastases Received previous treatment with HYCAMTIN. Subject has received an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to study entry Received prior radiation therapy for ovarian cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-arm<br>HYCAMTIN at a dose of 2.0 - 2.5mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1, every 21 days | Drug: topotecan<br>* HYCAMTIN at a dose of 2.0 mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1<br>Drug: CARBOPLATIN<br>* HYCAMTIN at a dose of 2.0 mg/m2 on Days 1 and 8 every 21 days followed by carboplatin at AUC 5 on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With the Indicated Response | Overall response rate, as determined by radiologic evaluation (utilizing the World Health Organization [WHO] criteria and/or physical examination was measured. Complete response (CR: complete disappearance of all lesions), partial response (PR: >50% decrease in the measurements of the largest lesions with no appearance of new lesions), stable disease (SD: no change in tumor size for at least 8 weeks) and progressive disease (PD: >25% increase in measurements of lesions or appearance of new lesions). | From start of treatment to evidence of CR or PR (up to 39.3 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Response | Time to response was calculated as the time from start of treatment until first evidence of partial response (PR; >50% decrease in the measurements of the largest lesions with no appearance of new lesions) or complete response (CR; complete disappearance of all lesions). | From start of treatment to evidence of PR or CR (up to 39.3 weeks) | 
| Duration of Response | Duration of response was calculated as the time from first documented PR or CR until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was censored. | From time of PR or CR to disease progression/death (up to 56.0 weeks) | 
| Progression-free Survival | Progression-free survival (PFS) was calculated as the time from the start of treatment until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was censored. Although Time to Disease Progression was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of PFS. As such, PFS was measured, not Time to Disease Progression. | From start of treatment to disease progression/death (up to 67.7 weeks) | 
| Number of Participants Who Died From the Start of Treatment to Follow-up | The number of participants who died from the start of treatment to follow-up was calculated. For participants who did not die, the date of last contact was used. The word used for such participants was censored. | From start of treatment to death (up to 110.4 weeks). | 
| The Number of Participants Classified as Responders in Cancer Antigen 125 (CA-125) | CA-125 is a tumor marker, found in greater concentration in tumor cells than other cells of the body. Participants were classed as responders if their CA-125 level at the end of study was 50% or less of baseline. In addition, a confirmatory sample (taken at least 28 days after the first sample) must have also been 50% or less of baseline. | Baseline to end of study (up to 54.7 weeks). | 
| Time to Disease Progression | Although Time to Disease Progression was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of Progression-free Survival. As such, Progression-free Survival was measured, not Time to Disease Progression. See the outcome measure entitled Progression-free Survival for data pertaining to time to disease progression. | From start of treatment to disease progression/death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HYCAMTIN, ovarian cancer, recurrent, relapsed, carboplatin, topotecan, potentially platinum-sensitive