paywalled: Epigenetic Resensitization to Platinum in Ovarian Cancer (low-dose decitabine/carboplatin)

Epigenetic Resensitization to Platinum in Ovarian Cancer
  
 "Together, the results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS."

Abstract

Preclinical studies have shown that hypomethylating agents reverse platinum resistance in ovarian cancer. In this phase II clinical trial, based upon the results of our phase I dose defining study, we tested the clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-resistant ovarian cancer patients. Among 17 patients with heavily pretreated and platinum-resistant ovarian cancer, the regimen induced a 35% objective response rate

Phase I Stereotactic Body Radiation for Metastatic or Recurrent Platinum-Resistant Ovarian Cancer - Full Text View - ClinicalTrials.gov

Phase I Stereotactic Body Radiation for Metastatic or Recurrent Platinum-Resistant Ovarian Cancer - Full Text View - ClinicalTrials.gov

Phase I Stereotactic Body Radiation for Metastatic or Recurrent Platinum-Resistant Ovarian Cancer

This study is currently recruiting participants.

Verified April 2012 by Stanford University

First Received on December 13, 2011.   Last Updated on April 18, 2012   History of Changes

Sponsor:	Stanford University
Information provided by (Responsible Party):	Stanford University
ClinicalTrials.gov Identifier:	NCT01494012

  Purpose

This phase I trial studies the side effects and the best dose of stereotactic body radiation therapy (SBRT) in treating patients with metastatic or recurrent ovarian cancer or primary peritoneal cancer. SBRT may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

abstract: A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: A gynecologic oncology group study

A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: A gynecologic oncology group study:

Background
Patients with recurrent ovarian cancer have limited options, especially in the context of relapse less than six months from primary platinum-based therapy. This Gynecologic Oncology Group (GOG) study was conducted to evaluate the impact of the histone deacetylase inhibitor, belinostat, in combination with carboplatin in women with platinum-resistant ovarian cancer.

Methods 
Eligible patients had measurable, recurrent disease within six months of their last dose of a platinum-based combination. Belinostat was dosed at 1000mg/m² daily for five days with carboplatin AUC 5 on day three of 21-day cycles. The primary endpoint was overall response rate (ORR), using a two-stage design.

Results
Twenty-nine women enrolled on study and 27 were evaluable. The median number of cycles given was two (range 1–10). One patient had a complete response and one had a partial response, for an ORR of 7.4% (95% CI, .9%–24.3%). Twelve patients had stable disease while eight had increasing disease. Response could not be assessed in five (18.5%). Grade 3 and 4 events occurring in more than 10% of treated patients were uncommon and limited to neutropenia (22.2%), thrombocytopenia (14.8%), and vomiting (11.1%). The median progression-free survival (PFS) was 3.3months and overall survival was 13.7months. PFS of at least six months was noted in 29.6% of patients. Due to the lack of drug activity, the study was closed after the first-stage.

Conclusions 
The addition of belinostat to carboplatin had little activity in a population with platinum-resistant ovarian cancer.