Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well giving cisplatin together with flavopiridol works in treating patients with advanced ovarian epithelial cancer or primary peritoneal cancer. Drugs used in chemotherapy, such as cisplatin and flavopiridol, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Detailed Description
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OBJECTIVES: I. Determine the response rate, time to progression, and survival in patients with advanced ovarian epithelial or primary peritoneal cancer treated with cisplatin and flavopiridol. II. Determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients are accrued to two separate groups (Group 2 closed to accrual as of 3/10/06) . GROUP 1: Patients receive cisplatin IV over 30 minutes and flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. GROUP 2 (Closed to accrual as of 3/10/06): Patients receive cisplatin IV over 30 minutes and flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for up to 3 years.

Official Title
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Phase II Trial of Flavopiridol and Cisplatin in Advanced Epithelial Ovarian and Primary Peritoneal Carcinomas

Conditions
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Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer, Stage IIIA Ovarian Epithelial Cancer, Stage IIIA Primary Peritoneal Cavity Cancer, Stage IIIB Ovarian Epithelial Cancer, Stage IIIB Primary Peritoneal Cavity Cancer, Stage IIIC Ovarian Epithelial Cancer, Stage IIIC Primary Peritoneal Cavity Cancer, Stage IV Ovarian Epithelial Cancer, Stage IV Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: alvocidib
* Drug: cisplatin/flavopiridol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed ovarian epithelial or primary peritoneal cancer: Advanced disease Meets at least 1 of the following criteria: Measurable disease; Evaluable disease plus CA 125 >= 2 times post-treatment nadir Treated with 1, and only 1, prior platin-containing chemotherapy regimen (e.g., paclitaxel or carboplatin-based) for ovarian epithelial or primary peritoneal cancer Prior treatment with the same regimen at first relapse allowed; No more than 3 total chemotherapy regimens allowed provided exactly 1 has been platin-containing; Must also have platin-resistant disease as defined for Group 1; Rechallenge with a single regimen upon progression after a hiatus from therapy counts as a single regimen Group 1, meeting 1 of the following criteria: Patients who relapse during or < 6 months after completion of post-debulking chemotherapy; Platinum sensitive patients in second relapse after having been treated/rechallenged with their initial regimen upon first relapse Group 2 (Closed to accrual as of 3/10/06): Patients who relapse >= 6 months after completion of post-debulking chemotherapy and are not retreated with the same or a different regimen No CNS metastases Performance status: ECOG 0-2 Hematopoietic: Absolute neutrophil count >= 1,500/mm3; Platelet count >= 100,000/mm3; Hemoglobin >= 10 g/dL (Note: May be supported with transfusion, epoetin alfa, or darbepoetin alfa) Hepatic: AST =< 2.5 times upper limit of normal (ULN); Alkaline phosphatase =< 2.5 times ULN; Bilirubin =< 1.5 times ULN Renal: Creatinine =< 1.5 times ULN Cardiovascular: No cardiac arrhythmia; No cardiac failure Not pregnant or nursing Negative pregnancy test More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) More than 3 weeks since prior radiotherapy Recovered from all prior therapy Fertile patients must use effective contraception No other malignancy within the past 5 years except non-melanoma skin cancer or carcinoma in situ of the cervix No diabetes No peripheral neuropathy >= grade 2 No baseline diarrhea (>= 4 stools/day) No uncontrolled infection No other concurrent uncontrolled serious medical condition No concurrent routine colony-stimulating factors

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Patients receive cisplatin IV over 30 minutes and flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Drug: alvocidib<br>* Given IV<br>* Other names: L-868275;Drug: cisplatin/flavopiridol<br>* Given IV<br>|
| Experimental: Group 2<br>Patients receive cisplatin IV over 30 minutes and flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Drug: alvocidib<br>* Given IV<br>* Other names: L-868275;Drug: cisplatin/flavopiridol<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Confirmed Tumor Responses Defined to be Either a Complete Response (CR) or Partial Response (PR) | A Complete Response (CR) is defined as the disappearance of all target lesions and normalization of tumor biomarkers. A Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4-6 weeks apart. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Will be estimated using the method of Kaplan-Meier. | Time from registration to date of last follow-up or death due to any cause, assessed up to 3 years | 
| Time to Progression | Time to progression will be estimated using the method of Kaplan-Meier. Progression is defined as having at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Time from registration to the date of progression or last follow-up, assessed up to 3 years |