Randomized Phase II Trial of Carboplatin and Paclitaxel with or without Lonafarnib in First-Line Treatment of Epithelial Ovarian Cancer Stage IIB-IV

Randomized Phase II Trial of Carboplatin and Paclitaxel with or without Lonafarnib in First-Line Treatment of Epithelial Ovarian Cancer Stage IIB-IV: Publication year: 2012

Source: Gynecologic Oncology


Objectives This study evaluates whether a molecular targeted therapy with the farnesyl transferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS).

Patients and Methods We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175mg/m2) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy.

Results 105 patients were recruited( 53 patients were randomised to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm:.....

Conclusion The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.

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.

PharmaLive: Topotarget Announces Updates on Belinostat in Two Clinical Trials - NSCLC and Ovarian Cancer (negative study ovarian/Belinostat/Carboplatin)

Ovarian cancer – GOG 0126-T (NCI-driven study)

Preliminary analysis of GOG 0126-T trial has not shown enough activity to enter into second stage. Consequently the study will be ended.

The study

The study is an open-label single-arm phase II trial with belinostat in combination with carboplatin given to patients with ovarian cancer who progress during or shortly after first-line treatment with platinum containing chemotherapy. The trial is sponsored by the GOG with support from the NCI. Belinostat is administered as a 30-minute daily IV infusion on day one through five with carboplatin being administered on day three. Treatment is given every third week and is repeated until disease progression......

Interleukin (IL)-18, a biomarker of human ovarian carcinoma, is predominantly released as biologically inactive precursor (negative study)