A Phase 3 Randomized Double-Blind, Placebo Controlled Trial of Genasense® Plus Dacarbazine vs. Dacarbazine Alone In Advanced Melanoma
The AGENDA Trial is the second randomized Phase 3 trial in advanced melanoma for Genasense®. The trial is designed to expand evidence for the safety and efficacy of Genasense® combined with dacarbazine for patients who have not previously been treated with chemotherapy. The study will prospectively target patients using a biomarker that identified patients who derived maximal benefit in the preceding trial of Genasense®, including significant increases in overall and progression-free survival.
Information for Physicians
AGENDA is a 300 patient randomized trial designed to expand evidence for the safety and efficacy of Genasense® combined with darcarbizine (DTIC) for patients who have not previously been treated with chemotherapy.
Genta is actively recruiting experienced investigative sites in Europe, Australia, and North America. For more information on the Genta clinical development program please contact us at
or 1-888-To-Genta (1-888-864-3682) or at clinicaltrials.gov at the following link:
AGENDA Study GM307: A multicenter, randomized, double-blind study of dacarbazine (DTIC) with or without Genasense® in chemotherapy-naïve subjects with advanced melanoma and low LDH.
Study rationale: We have previously completed a771 patient randomized phase III study of DTIC +/- Genasense®. In this study (GM301), LDH predicted for survival outcome; subjects in the prospectively defined subgroup of normal LDH (< 1.1 x ULN; n = 508) had a significant improvement in OS, as well as in PFS, ORR and durable RR with DTIC-Genasense® treatment. Among baseline LDH value of < 0.8 x ULN subjects (the lowest LDH category analyzed), the median OS was 12.3 months in the dacarbazine plus Genasense® group and 9.9 months in the dacarbazine-alone group (p = 0.0009). The current study, protocol GM307, seeks to confirm the findings from the earlier study and is being performed to prospectively assess the efficacy of DTIC plus Genasense® in chemotherapy-naïve subjects with advanced melanoma and baseline LDH < 0.8 x ULN.
Primary study objective: To compare the between treatment arm comparison of PFS and OS.
Secondary objectives: To compare the ORR, durable response, duration of response, and safety.
Study design: This study is a Phase III, multicenter, randomized (1:1), double-blind, placebo-controlled, parallel-group trial in chemotherapy-naïve subjects with advanced melanoma and LDH < 0.8 x ULN. A total of 300 subjects will be randomized to treatment with dacarbazine plus Genasense® or dacarbazine plus placebo. Protocol therapy and related testing will be completed in the outpatient setting. Inpatient treatment and testing are permitted at the discretion of the Investigator.
Subject eligibility: Patients who are chemotherapy naïve with progressive, histologically confirmed melanoma and have LDH < 0.8 x ULN, whose disease is either surgically unresectable or is metastatic (Stage IV), will be eligible. Patients with primary ocular or mucosal melanoma, bone-only metastatic disease and/or history or presence of brain metastasis or leptomeningeal disease will not be eligible.
Administration of study medications: Protocol therapy will be administered in 21-day cycles for up to 8 cycles. Subjects in the dacarbazine plus Genasense® group will receive Genasense® mg/kg/day by CIV on d1-5 (120 hours) plus dacarbazine 1000 mg/m2 as a 60-minute intravenous infusion immediately following the conclusion of the Genasense® infusion. Subjects in the dacarbazine plus placebo group will receive placebo by CIV d1-5 plus dacarbazine 1000 mg/m2 as a 60-minute intravenous infusion immediately following the conclusion of the placebo infusion. In both treatment groups, subjects who are responding or have stable disease after 8 cycles of therapy may, at the Investigator’s discretion, continue that same therapy for up to 8 additional cycles in Protocol GM307. Cross over will not be permitted.
Assessments: In the absence of progression, subjects will be followed every 2 months for PFS, RR and OS for 24 months from their date of randomization (OS only in the event of progression). Response (by RECIST) and tumor-related pain will be assessed Safety will be assessed based on AE reports and changes in clinical laboratory tests.
A Data Monitoring Board will review PFS, RR, OS and AE data beginning 6 months after the first subject is randomized and continuing every 6 months thereafter until the primary analysis of PFS is performed 6 months after randomization of the last subject.
For more information on the Genta clinical development program please contact us at
or 1-888-To-Genta (1-888-864-3682) or at clinicaltrials.gov at the following link:
Malignant melanoma is the most deadly form of skin cancer. The incidence of this disease is increasing by approximately 4% annually in the US.
The #1 cause of cancer death in women ages 25 to 301
Second most common cause of death, behind breast cancer, in women ages 30 to 351
Fastest growing cancer currently worldwide1
Most common cancer in young adults ages 20 to 301
Annual worldwide incidence of malignant melanoma is 132,000 with 66,000 people dying annually of melanoma and other skin cancers2
Accounts for 5% of all skin cancers and 71% of all skin cancer deaths1
Melanoma kills an estimated 94% of stage IV patients within 5 years of diagnosis3
Genasense®, Genta’s lead anticancer drug, is a novel targeted therapy that blocks the production of Bcl-2, a protein that appears to be a fundamental cause of cancer treatment resistance. By knocking down Bcl-2, Genasense® may enhance the effectiveness of chemotherapy in patients with advanced melanoma. Genta is committed to developing innovative products to better the lives of people with cancer.
AGENDA is a 300 patient randomized trial designed to expand evidence for the safety and efficacy of Genasense® combined with darcarbizine (DTIC) for patients who have not previously been treated with chemotherapy. The trial, is a randomized, double-blind, placebo-controlled study in which patients are randomly assigned to receive Genasense® plus dacarbazine (DTIC) or DTIC alone. AGENDA will be conducted at approximately 100 sites worldwide, including North America, Europe and Australia. Accrual is expected to take approximately 18 months, with initial data expected shortly thereafter.
If you or someone you know is interested in being a part of the AGENDA trial, please contact your physician.
More information about melanoma can be found at the following melanoma patient advocacy organizations web sites.
Clinical Development 
