Clinical trial NCT00462423
Conditions: Metastatic Malignant Melanoma
Keywords: Metastatic malignant melanoma First-line therapy
Sponsor: Lynn E. Spitler, MD
Start date: 2007-04-01; Completion date: 2012-01-01
Enrollment: 50 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The study is an open-label, single arm multicenter Phase II study to evaluate the safety and efficacy of the combination of Abraxane and Avastin as first-line therapy for patients with unresectable metastatic malignant melanoma. The patient sample will be approximately 50 individuals, males and females 18 years of age or older with measurable metastatic melanoma.

Patients will be treated with Abraxane administered weekly for 3 weeks via a 30-minute IV infusion at150 mg/m2 followed by 1 week rest (28-day cycle). Avastin will be administered in a dose of 10 mg/kg every 2 weeks (without rest period). Patients will be evaluated for disease progression every 2 months and those who do not have disease progression or unacceptable toxicity will be offered ongoing therapy until they have progressive disease or unacceptable toxicity.

Detailed description:
It has been suggested that chemotherapy administration may be synergistic with the effects of an antiangiogenic agent such as Avastin. A "Proof of Principal" of the concept of the synergistic effects of chemotherapy and antiangiogenic therapy has been shown in the favorable results reported with temozolomide administered in combination with thalidomide in melanoma, the favorable results reported for the use of FOLFOX4 in combination with Avastin in previously treated patients with advanced or metastatic colorectal cancer, and the approval of the combination of Avastin with 5-fluorouracil-based chemotherapy in the treatment of patients with metastatic carcinoma of the colon or rectum.

A number of lines of evidence suggest that the combination of Abraxane and Avastin may be effective as first-line therapy for melanoma:

* Taxanes are active agents in melanoma:

  1. In a clinical trial in patients who had failed combination chemotherapy (the Dartmouth regimen, there was a 24% response rate in patients treated with paclitaxel (in combination with tamoxifen).
  2. Paclitaxel is being used in a Phase III trial with carboplatin and Sorafenib in patients with metastatic melanoma who have failed no more than one previous systemic chemotherapeutic treatment.
  3. In a phase II trial of docetaxel in patients with metastatic melanoma, objective responses lasting more than 2 years were observed.
* Abraxane is a taxane that has efficacy superior to that of Taxol for the treatment of metastatic breast cancer. Abraxane was evaluated as first- and second-line therapy for patients with metastatic melanoma. Results were encouraging. In this study, Abraxane will be combined with Avastin in an effort to improve the clinical benefit and prolong the time to disease progression.

The primary end-point of the study is progression-free survival (PFS) at 4 months. Secondary end-points include progression-free survival, overall survival (OS), objective Response Rate (RR) in patients with measurable lesions, time to objective response, duration of objective response in patients with measurable lesions, and safety and tolerability of this combination.

Arms: arm 1: Single Arm, Open Label trial of Abraxane and Avastin
Interventions: intervention 1: Avastin intervention 2: Abraxane
Intervention descriptions: intervention 1: Avastin 10 mg/kg IV every 2 weeks (without rest period). intervention 2: Abraxane 150 mg/m2 IV weekly for 3 weeks of a 28-day cycle.

Protocol documents: