Entry Detail
| General information | |
| Database: | DB00533 |
| Objective: | Patients with recurrent ovarian cancer have limited options, especially in the context of relapse less than six months from primary platinumbased 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 platinumresistant ovarian cancer. |
| Authors: | Hyman DM, et al |
| Title: | Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. |
| Journal: | N Engl J Med. |
| Year: | 2015 |
| PMID: | 26287849 |
| Trial Design | |
| Clinical Trial Id: | NCT01524978 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | vemurafenib+ cetuximab |
| Study Type: | phase II basket study |
| Key Patients Feature: | BRAF V600 mutations were identified by means of mutational analysis assays routinely performed at each participating site. Additional key eligibility criteria were measurable disease, according to Response Evaluation Criteria in Solid Tumors(RECIST), version 1.1 and an Eastern Cooperative Oncology Group (ECOG) performancestatus score of 0 to 2 (on a 5point scale, withlarger numbers indicating greater disability). |
| Biomarker: | BRAF V600 mutationpositive |
| Biomark Analysis: | BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. |
| Control Group Info: | single arm |
| Treatment Info: | A standard 3+3 doseescalation design (three to six patients per cohort and up to three dose levels tested) was used to establish the recommended (maximum tolerated) combination dose. An additional cohort of patients with colorectal cancer received vemurafenib and cetuximab at the recommended combination dose (960 mg of vemurafenib administered orally twice daily and an intravenous loading dose of 400 mg of cetuximab per square meter of bodysurface area, followed by aweekly intravenous dose of 250 mg per square meter), and the safety and efficacy were assessed. All other patients received vemurafenib alone at an oral dose of 960 mg twice daily. |
| Primary End Point: | response rate |
| Secondary End Point: | progression free and overall survival |
| Patients Number: | 29 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | In the cohort with non small cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67); |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.3 months (95% CI, 3.5 to 10.8). |
| Median OS A vs. C: | The median overall survival has not yet been reached; the preliminary 12month overall survival rate was 66% (95% CI, 36 to 85). |
| Adverse Event(agent arm): | Overall, safety data for vemurafenib monotherapy were similar to data from previous studies of vemurafenib in cutaneous melanoma, although samples sizes within individual cohorts were too small to allow a definitive comparison.25 The most common adverse events among all patients receiving vemurafenib monotherapy were rash (68% of patients), fatigue (56%), and arthralgia (40%). |
| Conclusions: | The addition of belinostat to carboplatin had little activity in a population with platinumresistant ovarian cancer. |