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

Phase 2

Completed

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

Interventions: Drug: cisplatin
Drug: alvocidib
Drug: cisplatin/flavopiridol

Registration Number: NCT00083122

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 45

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	cisplatin/flavopiridol	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	alvocidib	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	cisplatin/flavopiridol	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	cisplatin	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 1	cisplatin	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 1	alvocidib	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Confirmed Tumor Responses Defined to be Either a Complete Response (CR) or Partial Response (PR)	24 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Time from registration to date of last follow-up or death due to any cause, assessed up to 3 years	Will be estimated using the method of Kaplan-Meier.
Time to Progression	Time from registration to the date of progression or last follow-up, assessed up to 3 years	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.