Vorinostat, Carboplatin and Gemcitabine in Women With Recurrent, Platinum-Sensitive Ovarian Cancer

Stopped early · Phase 1/Phase 2

Conditions studied: Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer

In brief

This trial is a Phase Ib/II study of carboplatin/gemcitabine/vorinostat for the treatment of platinum sensitive recurrent ovarian cancer. The carboplatin and gemcitabine combination is an FDA approved regimen for platinum-sensitive recurrent ovarian cancer. 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.The purpose of the Phase Ib study is to determine the highest dose of the drug vorinostat that can be given safely in combination with carboplatin and gemcitabine. Not everyone who participates in this research study will receive the same dose of the study drug, vorinostat, but carboplatin and gemcitabine doses are held constant. Vorinostat doses depend on previous enrollment and tolerability. The expansion Phase II study uses the vorinostat dose found in the Phase Ib study in combination with carboplatin/gemcitabine and as a single agent maintenance therapy to better understand toxicity and efficacy.

Key facts

Study ID: NCT00910000
Run by: Dana-Farber Cancer Institute
People needed: 15
Starts: 2009-06-01
Expected to finish: 2015-10-01
Last updated by the study team: 2018-09-10

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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

Where it is running

Massachusetts General Hospital — Boston, Massachusetts, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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