NCT00779714

Comparative Study of Individualized Sensitivity-Directed Chemotherapy Versus DTIC

Prospectively Randomized Phase III Study of an Individualized Sensitivity-Directed Combination Chemotherapy Versus DTIC as First-Line Treatment in Stage IV Metastatic Melanoma

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 360 (estimated)
• Sponsor: University of Wuerzburg · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial is aimed to investigate the efficacy of an individualized, sensitivity-directed combination chemotherapy in comparison to the standard regimen DTIC. Two question are aimed to be answered by this study: 1. Is the individual chemosensitivity index (BICSI) a prognostic / predictive biomarker for chemotherapy ? 2. Is an individualized, sensitivity-directed combination chemotherapy superior to the standard regimen DTIC in terms of survival and response ?

Detailed description

Melanoma is a cutaneous neoplasm known for its high aggressiveness, its early dissemination of metastases, and its poor prognosis once metastasized. Chemotherapy with dacarbacine (DTIC) is widely accepted as the standard treatment in metastatic melanoma, with reported response rates of about 10%. This poor outcome is assumed to be due to a high chemoresistance intrinsic to melanoma cells. However, other therapeutic options like polychemotherapy, biochemotherapy, immunotherapy as well as targeted agents did not yet prove to be superior to DTIC in multicenter randomized studies. Therefore, chemotherapy still is considered as the main therapeutic option in advanced metastatic melanoma, and a number of non-standard chemotherapeutics have been tested in small pilot studies to improve treatment efficacy. Even though complete remissions of metastatic lesions could only be observed in a few patients, these observations indicate a subgroup of patients exhibiting high sensitivity to certain anticancer drugs. An in vitro ATP-based chemosensitivity assay has been shown to differentiate between chemosensitive and chemoresistant melanoma patients. A phase-II-study testing this assay in 53 metastatic melanoma patients followed by a sensitivity-directed individualized chemotherapy demonstrated, that the chemosensitivity profile of an individual patient, reflected by the best individual chemosensitivity index (BICSI), correlated with therapy outcome in terms of therapy response and patient overall survival (Ugurel S: Clin Cancer Res 2006). Interestingly, a surprisingly high proportion of about 2/5 of the investigated patient cohort were classified as chemosensitive, the remaining 3/5 were classified as chemoresistant. Objective response was 36.4% in chemosensitive patients compared to 16.1% in chemoresistant patients (p=0.114); progression arrest (CR+PR+SD) was 59.1% versus 22.6% (p=0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared to 7.4 months in chemoresistant patients (p=0.041). These encouraging results prompted the initiation of this randomized phase-III-trial investigating an individualized sensitivity-directed combination chemotherapy compared to the current standard treatment DTIC, as first-line treatment in metastatic melanoma. The therapeutics for chemosensitivity testing and treatment of patients were chosen considering the results of the phase-II-trial (paclitaxel+cisplatinum, treosulfan+cytarabine).

Conditions

• Melanoma

Interventions

Type	Name	Description
DRUG	DTIC (dacarbazine)	1000 mg/m2, d1 every 21 days
DRUG	paclitaxel + cisplatin	paclitaxel 200 mg/m2 cisplatin 50 mg/m2 d1 every 21 days
DRUG	treosulfan + cytarabine	treosulfan 2500 mg/m2, d2 cytarabine 100 mg/m2, d1-3 every 21 days

Timeline

• Start date: 2008-10-01
• Primary completion: 2012-10-01
• Completion: 2013-04-01
• First posted: 2008-10-24
• Last updated: 2008-10-24

Locations

23 sites across 1 country: Germany