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

Browse trials for

• Ovarian Neoplasms 2,695
• Carcinoma, Ovarian Epithelial 1,617
• Fallopian Tube Neoplasms 720

Keywords

• carboplatin
• gemcitabine
• vorinostat

Ovarian Neoplasms

2,695 studies on the registry are indexed under Ovarian Neoplasms; 727 are open to participants now.

This study's enrollment of 15 is below the median of 60 across 2,030 interventional studies indexed under Ovarian Neoplasms.

Lead sponsor

Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.

Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.

Study arms

• Experimental
  Dose Level 1A

  Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

  Drug: Vorinostat · Drug: Carboplatin · Drug: Gemcitabine

• Experimental
  Dose Level 2A

  Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

  Drug: Vorinostat · Drug: Carboplatin · Drug: Gemcitabine

• Experimental
  Dose Level 1B

  Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of every three week cycle Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

  Drug: Vorinostat · Drug: Carboplatin · Drug: Gemcitabine

• Experimental
  Dose Level 1C

  Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of every three week cycle Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

  Drug: Vorinostat · Drug: Carboplatin · Drug: Gemcitabine

• Experimental
  Dose Level 1D

  Vorinostat: 300mg, taken orally once a day for days 1 and 2 of every three week cycle Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

  Drug: Vorinostat · Drug: Carboplatin · Drug: Gemcitabine

• Experimental
  Dose Level 2D

  Vorinostat: 400mg, taken orally once a day for days 1 and 2 of every three week cycle Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.

  Drug: Vorinostat · Drug: Carboplatin · Drug: Gemcitabine

Interventions

• DrugVorinostat

  Also known as: Zolinza

• DrugCarboplatin

  Also known as: paraplatin

• DrugGemcitabine

  Also known as: Gemzar

Primary outcomes

1. Vorinostat Maximum Tolerated Dose (MTD) [Phase Ib]

   The Vorinostat MTD is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.

   Time frame: The DLT observation period in determining the MTD was the 21-day cycle 1 length.

2. Dose Limiting Toxicity (DLT) [Phase Ib]

   Dose-limiting toxicity was based on the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) and defined as any of the following: 1. Any CTCAE grade 3 or 4 non-hematologic event except manageable gastrointestinal toxicity and fatigue. 2. Any of the following hematologic events (excluding neutropenia lasting \< 5 days): i) febrile neutropenia defined as grade 3-4 neutropenia with fever ≥ 38.5°C and/or infection. ii) any grade 4 neutropenia lasting 5 days or more. iii) grade 4 thrombocytopenia (plt count \< 25x 109/L) iv) failure of ANC to recover to ≥ 1000/μL or platelets to recover to ≥ 50,000/μL within 14 days of therapy v) grade 4 anemia 3. Any clinically significant abnormal laboratory value that results in dose delay of \>14 days. 4. \<75% of vorinostat dosing taken by the patient during the first cycle due to any toxicity.

   Time frame: The DLT observation period in determining the MTD was the 21-day cycle 1 length.

Secondary outcomes

1. Response

   Response was based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD from the smallest LD recorded on treatment. Stable disease (SD) is neither sufficient increase to qualify as PD nor sufficient shrinkage to qualify for PR. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed 4 weeks +/- 2 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Participants who received therapy but did not have their disease re-evaluated were considered unevaluable.

   Time frame: Disease was assessed radiographically (CT or MRI scan) every 2 cycles on treatment; Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).

Baseline characteristics

Publications

• Matulonis U, Berlin S, Lee H, Whalen C, Obermayer E, Penson R, Liu J, Campos S, Krasner C, Horowitz N. Phase I study of combination of vorinostat, carboplatin, and gemcitabine in women with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer. Cancer Chemother Pharmacol. 2015 Aug;76(2):417-23. doi: 10.1007/s00280-015-2813-9. Epub 2015 Jun 29. PubMed 26119093 ↗

Individual participant data

Plan to share: No