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
Conditions
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.
Interventions
DRUGcisplatin
Given IV
DRUGalvocidib
Given IV
DRUGcisplatin/flavopiridol
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Forty-five patients were enrolled between December 23, 2004 and February 25, 2010: 40 patients to Group 1 (platin resistant; 14 evaluable, 26 measurable) and 5 patients to Group 2 (platin sensitive; 1 evaluable, 4 measurable). Group 2 was closed on 03/10/2006 due to poor accrual.
Pre-assignment details
Participants who progressed or relapsed during or within 6 months of primary platinum-based therapy constituted Group 1 (Platin Resistant). Participants who relapsed \> 6 months following completion of platinum-based therapy, and who had received only a single prior chemotherapy regimen constituted Group 2 (Platin Sensitive).
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Platin Resistant) Patients receive cisplatin IV over 2 hours and flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | 40 |
| Group 2 (Platin Sensitive) Patients receive cisplatin IV over 2 hours and flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | 5 |
| Total | 45 |
Baseline characteristics
| Characteristic | Group 1 (Platin Resistant) | Group 2 (Platin Sensitive) | Total |
|---|---|---|---|
| Age, Continuous | 59 years | 61 years | 59 years |
| Region of Enrollment United States | 40 participants | 5 participants | 45 participants |
| Sex: Female, Male Female | 40 Participants | 5 Participants | 45 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 45 / 45 |
| serious Total, serious adverse events | 23 / 45 |
Outcome results
Primary
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.
Time frame: 24 weeks
Population: All 45 participants were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (Platin Resistant) | Proportion of Confirmed Tumor Responses Defined to be Either a Complete Response (CR) or Partial Response (PR) | Partial Response (PR) | 15 Percentage of Participants |
| Group 1 (Platin Resistant) | Proportion of Confirmed Tumor Responses Defined to be Either a Complete Response (CR) or Partial Response (PR) | Complete Response (CR) | 2.5 Percentage of Participants |
| Group 2 (Platin Sensitive) | Proportion of Confirmed Tumor Responses Defined to be Either a Complete Response (CR) or Partial Response (PR) | Complete Response (CR) | 0 Percentage of Participants |
| Group 2 (Platin Sensitive) | Proportion of Confirmed Tumor Responses Defined to be Either a Complete Response (CR) or Partial Response (PR) | Partial Response (PR) | 40 Percentage of Participants |
Secondary
Overall Survival
Will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to date of last follow-up or death due to any cause, assessed up to 3 years
Population: All 40 participants in Group 1 were analyzed for this primary endpoint. However, due to the low accrual and early group 2 closure, Group 2 was not statistically evaluated for this endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Platin Resistant) | Overall Survival | 17.5 months |
Secondary
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 frame: Time from registration to the date of progression or last follow-up, assessed up to 3 years
Population: All 40 participants from Group 1 were analyzed. However, due to slow accrual and early closure, Group 2 was not statistically analyzed for this endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1 (Platin Resistant) | Time to Progression | 4.3 months |