Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer
Study Details
Study Description
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:
-
Determine the response rate, time to progression, and survival in patients with advanced ovarian epithelial or primary peritoneal cancer treated with cisplatin and flavopiridol.
-
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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. |
Drug: cisplatin
Given IV
Other Names:
Drug: alvocidib
Given IV
Other Names:
Drug: cisplatin/flavopiridol
Given IV
|
Experimental: Group 2 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
Given IV
Other Names:
Drug: alvocidib
Given IV
Other Names:
Drug: cisplatin/flavopiridol
Given IV
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Keith Bible, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00029
- NCI-2009-00029
- CDR0000363562
- MC0261
- 5876
- N01CM62205
- P30CA015083
Study Results
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 Detail | 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"). |
Arm/Group Title | Group 1 (Platin Resistant) | Group 2 (Platin Sensitive) |
---|---|---|
Arm/Group Description | Patients receive 60 mg/m^2 of cisplatin IV over 2 hours and 100 mg/m^2 flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Patients receive 60 mg/m^2 of cisplatin IV over 2 hours and 100 mg/m^2 flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
Period Title: Overall Study | ||
STARTED | 40 | 5 |
COMPLETED | 40 | 5 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Group 1 (Platin Resistant) | Group 2 (Platin Sensitive) | Total |
---|---|---|---|
Arm/Group Description | 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. | 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. | Total of all reporting groups |
Overall Participants | 40 | 5 | 45 |
Age (years) [Median (Full Range) ] | |||
Median (Full Range) [years] |
59
|
61
|
59
|
Sex: Female, Male (Count of Participants) | |||
Female |
40
100%
|
5
100%
|
45
100%
|
Male |
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | |||
United States |
40
100%
|
5
100%
|
45
100%
|
Outcome Measures
Title | Proportion of Confirmed Tumor Responses Defined to be Either a Complete Response (CR) or Partial Response (PR) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
All 45 participants were analyzed. |
Arm/Group Title | Group 1 (Platin Resistant) | Group 2 (Platin Sensitive) |
---|---|---|
Arm/Group Description | Patients receive 60 mg/m^2 cisplatin IV over 2 hours and 100 mg/m^2 flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Patients receive 60 mg/m^2 cisplatin IV over 2 hours and 100 mg/m^2 flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
Measure Participants | 40 | 5 |
Complete Response (CR) |
2.5
6.3%
|
0
0%
|
Partial Response (PR) |
15
37.5%
|
40
800%
|
Title | Overall Survival |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Group 1 (Platin Resistant) | Group 2 (Platin Sensitive) |
---|---|---|
Arm/Group Description | Patients receive 60 mg/m^2 cisplatin IV over 2 hours and 100 mg/m^2 flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Patients receive 60 mg/m^2cisplatin IV over 2 hours and 100 mg/m^2 flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
Measure Participants | 40 | 0 |
Median (95% Confidence Interval) [months] |
17.5
|
Title | Time to Progression |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Group 1 (Platin Resistant) | Group 2 (Platin Sensitive) |
---|---|---|
Arm/Group Description | Patients receive 60 mg/m^2 cisplatin IV over 2 hours and 100 mg/m^2 flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Patients receive 60 mg/m^2 cisplatin IV over 2 hours and 100 mg/m^2 flavopiridol IV over 24 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
Measure Participants | 40 | 0 |
Median (95% Confidence Interval) [months] |
4.3
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Group 1 and Group 2 Combined | |
Arm/Group Description | 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. | |
All Cause Mortality |
||
Group 1 and Group 2 Combined | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Group 1 and Group 2 Combined | ||
Affected / at Risk (%) | # Events | |
Total | 23/45 (51.1%) | |
Cardiac disorders | ||
Arrhythmia | 1/45 (2.2%) | 1 |
Atrial fibrillation | 1/45 (2.2%) | 1 |
Ear and labyrinth disorders | ||
Hearing impaired | 1/45 (2.2%) | 1 |
Tinnitus | 1/45 (2.2%) | 1 |
Gastrointestinal disorders | ||
Abdominal pain | 2/45 (4.4%) | 2 |
Diarrhea | 1/45 (2.2%) | 1 |
Nausea | 4/45 (8.9%) | 4 |
Small intestinal obstruction | 3/45 (6.7%) | 3 |
Vomiting | 3/45 (6.7%) | 3 |
General disorders | ||
Chest pain | 1/45 (2.2%) | 1 |
Fatigue | 2/45 (4.4%) | 2 |
Fever | 2/45 (4.4%) | 3 |
Hepatobiliary disorders | ||
Gallbladder obstruction | 1/45 (2.2%) | 1 |
Immune system disorders | ||
Hypersensitivity | 3/45 (6.7%) | 3 |
Infections and infestations | ||
Pneumonia | 1/45 (2.2%) | 1 |
Investigations | ||
Creatinine increased | 1/45 (2.2%) | 1 |
Neutrophil count decreased | 1/45 (2.2%) | 1 |
Metabolism and nutrition disorders | ||
Dehydration | 4/45 (8.9%) | 4 |
Serum magnesium decreased | 2/45 (4.4%) | 2 |
Serum phosphate decreased | 1/45 (2.2%) | 1 |
Serum potassium decreased | 2/45 (4.4%) | 2 |
Serum sodium decreased | 1/45 (2.2%) | 1 |
Nervous system disorders | ||
Ataxia | 1/45 (2.2%) | 1 |
Syncope | 2/45 (4.4%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||
Dyspnea | 1/45 (2.2%) | 1 |
Skin and subcutaneous tissue disorders | ||
Pruritus | 1/45 (2.2%) | 1 |
Skin disorder | 1/45 (2.2%) | 1 |
Sweating | 1/45 (2.2%) | 1 |
Vascular disorders | ||
Hypertension | 1/45 (2.2%) | 1 |
Thrombosis | 2/45 (4.4%) | 2 |
Other (Not Including Serious) Adverse Events |
||
Group 1 and Group 2 Combined | ||
Affected / at Risk (%) | # Events | |
Total | 45/45 (100%) | |
Blood and lymphatic system disorders | ||
Hemoglobin decreased | 42/45 (93.3%) | 179 |
Cardiac disorders | ||
Palpitations | 2/45 (4.4%) | 2 |
Ear and labyrinth disorders | ||
Hearing impaired | 2/45 (4.4%) | 3 |
Hearing test abnormal | 1/45 (2.2%) | 1 |
Tinnitus | 3/45 (6.7%) | 15 |
Gastrointestinal disorders | ||
Abdominal pain | 1/45 (2.2%) | 1 |
Colitis | 1/45 (2.2%) | 1 |
Constipation | 3/45 (6.7%) | 7 |
Diarrhea | 31/45 (68.9%) | 123 |
Dry mouth | 1/45 (2.2%) | 2 |
Dyspepsia | 2/45 (4.4%) | 4 |
Ear, nose and throat examination abnormal | 1/45 (2.2%) | 1 |
Gastritis | 1/45 (2.2%) | 5 |
Mucositis oral | 5/45 (11.1%) | 5 |
Nausea | 42/45 (93.3%) | 153 |
Vomiting | 32/45 (71.1%) | 93 |
General disorders | ||
Fatigue | 44/45 (97.8%) | 165 |
Pain | 2/45 (4.4%) | 7 |
Infections and infestations | ||
Urinary tract infection | 1/45 (2.2%) | 1 |
Injury, poisoning and procedural complications | ||
Vascular access complication | 1/45 (2.2%) | 1 |
Investigations | ||
Alanine aminotransferase increased | 1/45 (2.2%) | 1 |
Alkaline phosphatase increased | 15/45 (33.3%) | 37 |
Aspartate aminotransferase increased | 9/45 (20%) | 15 |
Blood bilirubin increased | 1/45 (2.2%) | 1 |
Creatinine increased | 12/45 (26.7%) | 29 |
Leukocyte count decreased | 14/45 (31.1%) | 30 |
Neutrophil count decreased | 33/45 (73.3%) | 59 |
Platelet count decreased | 28/45 (62.2%) | 90 |
Weight loss | 3/45 (6.7%) | 3 |
Metabolism and nutrition disorders | ||
Anorexia | 12/45 (26.7%) | 18 |
Blood glucose increased | 32/45 (71.1%) | 74 |
Blood uric acid increased | 1/45 (2.2%) | 1 |
Dehydration | 2/45 (4.4%) | 2 |
Serum albumin decreased | 7/45 (15.6%) | 11 |
Serum calcium decreased | 6/45 (13.3%) | 9 |
Serum calcium increased | 1/45 (2.2%) | 2 |
Serum magnesium decreased | 24/45 (53.3%) | 77 |
Serum magnesium increased | 2/45 (4.4%) | 2 |
Serum phosphate decreased | 2/45 (4.4%) | 2 |
Serum potassium decreased | 11/45 (24.4%) | 13 |
Serum potassium increased | 1/45 (2.2%) | 1 |
Serum sodium decreased | 10/45 (22.2%) | 21 |
Musculoskeletal and connective tissue disorders | ||
Back pain | 1/45 (2.2%) | 1 |
Myalgia | 1/45 (2.2%) | 1 |
Neck pain | 1/45 (2.2%) | 1 |
Pain in extremity | 1/45 (2.2%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Tumor pain | 1/45 (2.2%) | 1 |
Nervous system disorders | ||
Dizziness | 1/45 (2.2%) | 1 |
Dysgeusia | 2/45 (4.4%) | 5 |
Extrapyramidal disorder | 1/45 (2.2%) | 2 |
Headache | 3/45 (6.7%) | 4 |
Peripheral motor neuropathy | 3/45 (6.7%) | 10 |
Peripheral sensory neuropathy | 33/45 (73.3%) | 114 |
Psychiatric disorders | ||
Anxiety | 1/45 (2.2%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 1/45 (2.2%) | 1 |
Dyspnea | 1/45 (2.2%) | 1 |
Hiccups | 1/45 (2.2%) | 6 |
Skin and subcutaneous tissue disorders | ||
Alopecia | 9/45 (20%) | 11 |
Body odor | 1/45 (2.2%) | 1 |
Rash acneiform | 2/45 (4.4%) | 8 |
Vascular disorders | ||
Hypertension | 1/45 (2.2%) | 1 |
Thrombosis | 4/45 (8.9%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Keith C. Bible, M.D, Ph.D. |
---|---|
Organization | Mayo Clinic Cancer Center |
Phone | |
Bible.Keith@mayo.edu |
- NCI-2009-00029
- NCI-2009-00029
- CDR0000363562
- MC0261
- 5876
- N01CM62205
- P30CA015083