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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00083122
Collaborator
(none)
45
1
2
97
0.5

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:
  1. Determine the response rate, time to progression, and survival in patients with advanced ovarian epithelial or primary peritoneal cancer treated with cisplatin and flavopiridol.

  2. 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

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Trial of Flavopiridol and Cisplatin in Advanced Epithelial Ovarian and Primary Peritoneal Carcinomas
Study Start Date :
Apr 1, 2004
Actual Primary Completion Date :
Jul 1, 2010
Actual Study Completion Date :
May 1, 2012

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:
  • CACP
  • CDDP
  • CPDD
  • DDP
  • Drug: alvocidib
    Given IV
    Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
  • 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:
  • CACP
  • CDDP
  • CPDD
  • DDP
  • Drug: alvocidib
    Given IV
    Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
  • Drug: cisplatin/flavopiridol
    Given IV

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts 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

    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.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00083122
    Other Study ID Numbers:
    • NCI-2009-00029
    • NCI-2009-00029
    • CDR0000363562
    • MC0261
    • 5876
    • N01CM62205
    • P30CA015083
    First Posted:
    May 17, 2004
    Last Update Posted:
    May 21, 2014
    Last Verified:
    Apr 1, 2013

    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

    1. Primary Outcome
    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%
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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

    [Not Specified]

    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
    Email Bible.Keith@mayo.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00083122
    Other Study ID Numbers:
    • NCI-2009-00029
    • NCI-2009-00029
    • CDR0000363562
    • MC0261
    • 5876
    • N01CM62205
    • P30CA015083
    First Posted:
    May 17, 2004
    Last Update Posted:
    May 21, 2014
    Last Verified:
    Apr 1, 2013