Vorinostat, Carboplatin and Gemcitabine Plus Vorinostat Maintenance in Women With Recurrent, Platinum-Sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer

This study has been terminated.
(Terminated due to unacceptable toxicity)
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Ursula A. Matulonis, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00910000
First received: May 26, 2009
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

The purpose of this research study is to: 1) Determine the highest dose of the drug vorinostat that can be given safely in combination with carboplatin and gemcitabine and 2) determine how long the participant's cancer will respond to the combination of vorinostat, carboplatin and gemcitabine. Vorinostat is a type of drug called a histone deacetylase inhibitor (HDAC inhibitor). HDAC inhibitors interact with chromosomes in the cancer cell and cause cancer cells to stop growing. Vorinostat has shown a decrease in the amount of ovarian cancer cells growing in the laboratory and also may enhance the anti-cancer effects of carboplatin.


Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Drug: Vorinostat
Device: Carboplatin
Drug: Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IB/II Study of Combination Vorinostat, Carboplatin and Gemcitabine + Vorinostat Maintenance in Women With Recurrent, Platinum-Sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Determine the maximally tolerated dose (MTD) of vorinostat when combined with fixed dose, standard carboplatin/gemcitabine in patients wtih recurrent platinum-sensitive epithelial ovarian cancer. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Estimate the median progression-free survival (PFS) for this population in a phase II expansion cohort of patients treated with carboplatin/vorinostat and vorinostat maintenance. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Estimate the response rate of vorinostat plus carboplatin/gemcitabine via GCIG CA125 criteria or via RECIST criteria in this patient population. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Assess the toxicities of carboplatin/gemcitabine plus vorinostat [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Measure the overall survival (OS) and progression-free survival and progression-free survival (PFS) in this patient population [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: June 2009
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level 1 Drug: Vorinostat
Taken orally once a day in the AM for the first two weeks of each three-week cycle. Dose will depend upon when participant enters into the clinical trial
Device: Carboplatin
Given intravenously on day 1 of every three week cycle
Drug: Gemcitabine
Given intravenously on day and day 8 of every three week cycle
Experimental: Dose Level 2 Drug: Vorinostat
Taken orally once a day in the AM for the first two weeks of each three-week cycle. Dose will depend upon when participant enters into the clinical trial
Device: Carboplatin
Given intravenously on day 1 of every three week cycle
Drug: Gemcitabine
Given intravenously on day and day 8 of every three week cycle
Experimental: Dose Level 3 Drug: Vorinostat
Taken orally once a day in the AM for the first two weeks of each three-week cycle. Dose will depend upon when participant enters into the clinical trial
Device: Carboplatin
Given intravenously on day 1 of every three week cycle
Drug: Gemcitabine
Given intravenously on day and day 8 of every three week cycle

Detailed Description:
  • The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects. Not everyone who participates in this research study will receive the same dose of the study drug, vorinostat. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses. There are 3 dose levels for vorinostat that are being tested.
  • Each treatment cycle lasts three weeks or 21 days. The carboplatin and gemcitabine chemotherapy will be administered as per the FDA approved doses. The carboplatin will be administered on day 1 through the vein and gemcitabine will be administered intravenously on day 1 and day 8. Participants will receive up to 8 cycles of chemotherapy, as determined by the participant and their doctor, depending on how well the cancer is responding and what side effects the participant is experiencing.
  • Participants will take the study medication, vorinostat, by mouth, once a day in the morning beginning on day 1 of the cycle. Participants will take the vorinostat for the first two weeks (14 days) of each cycle. The 3rd week of the cycle, participants will not take the study drug vorinostat.
  • Physical exams will be performed regularly while participants are on this study.
  • Participants cancer will be assessed during treatment while on this study. If participants CA125 value is elevated, the investigators will follow the cancer by the CA125 blood test every 2 cycles. If the cancer is only visible on CT or MRI scan and the CA125 blood test is not elevated, regular assessment of the cancer (every 2 cycles of chemotherapy) by CT or MRI scan will also occur. Once the chemotherapy has been completed, a CT or MRI scan will be performed on all participants to determine if they are eligible to continue on the study and receive vorinostat maintenance.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed recurrent epithelial ovarian cancer, fallopian tube cancer, or peritoneal cancer
  • Must have received a platinum-based chemotherapy regimen at initial diagnosis
  • Patients with primary platinum-sensitive (defined as a cancer initially platinum-sensitive followed by a progression-free interval from first exposure to platinum of 6 months or greater) recurrent ovarian, tubal or peritoneal cancer
  • Must have an elevated CA125 (twice the ULN) within 2 weeks of enrolling on study (2 pretreatment measurements that are twice the upper limits of institutional normal and are drawn at least 1 day but not more than 14 days apart). At least one of the samples should be checked within one week of starting treatment. Measurable cancer via RECIST criteria via CT or MRI scan is not required but if clinically indicated will be monitored.
  • For patients who do not have an elevated CA125 (twice the ULN), participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan.
  • 18 years of age or older
  • Life expectancy of greater than 16 weeks
  • ECOG Performance Status 0, 1, or 2
  • Participants must have normal organ and marrow function as outlined in the protocol
  • Patients could have received up to 1 prior non-platinum chemotherapy regimen in the recurrent setting (anti-angiogenic agents and other phase II non-hormonal therapies used to treat recurrent cancer count as a prior non-platinum therapy) but only one prior platinum (used to treat initial diagnosis). Patients may received up to 2 prior hormonal therapies.
  • Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation
  • Must be able and willing to take oral medications
  • No clinical nor radiographic evidence of an existing or impending bowel obstruction
  • Should be at least 2 weeks from any surgical procedure, with the exception of minor surgery, such as port placement
  • Patients who have known carboplatin hypersensitivity reaction can receive carboplatin if they are followed by an allergist, follow a published hypersensitivity desensitization protocol when receiving carboplatin, and agree to receive carboplatin under these circumstances
  • Patients taking valproic acid for epilepsy may enroll if they discontinue valproic acid 30 days prior to enrolling for washout
  • Patients must have a normal QTc interval and no history of QTc prolongation on EKG

Exclusion Criteria:

  • Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • May not be receiving any other investigational agent
  • Participants with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, pulmonary disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breastfeeding women
  • Individuals with a history of different malignancy are ineligible except for the following circumstances: disease-free for at least 5 years and are deemed by the investigator to be a low risk for recurrence of that malignancy; cervical cancer in situ, concurrent stage IA and grade I endometrial cancer, and basal cell or squamous cell carcinoma of the skin
  • Patients taking valproic acid unless valproic acid is stopped at least 30 days prior to enrollment
  • Receipt in the past of any other HDAC inhibitor for treatment of any malignancy
  • Receipt of radiation therapy to >25% of bone marrow-bearing areas
  • Patients who have gastrointestinal disorders likely to interfere with absorption of vorinostat
  • Known active HIV or hepatitis viral infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00910000

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Ursula A. Matulonis, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Ursula A. Matulonis, MD, Medical Director, Gynecologic Oncology, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00910000     History of Changes
Other Study ID Numbers: 09-026
Study First Received: May 26, 2009
Last Updated: June 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
carboplatin
gemcitabine
vorinostat

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Gemcitabine
Vorinostat
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014