A multicenter, randomized, double-blind study of dacarbazine with or without Genasense in chemotherapy naïve subjects with advanced melanoma and low LDH (The AGENDA Trial)

Conditions: Advanced melanoma
MedDRA version: 12.1Level: LLTClassification code 10027480Term: Metastatic malignant melanoma

Registration Number: EUCTR2007-003340-30-AT

Lead Sponsor: Genta Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 325

Inclusion Criteria

The following criteria must be met before registration not more than 15 days prior to randomisation:
1. Histologically confirmed diagnosis of melanoma
2. Progressive disease that is not surgically resectable, or metastatic Stage IV disease
3. LDH 4. Chemotherapy naïve Note: Prior immunotherapy, radiotherapy, or cytokine, biologic, or vaccine therapy is permitted.
5. Measurable disease defined as at least 1 tumor lesion that can be accurately and serially measured in at least 1 dimension (longest diameter to be recorded) and is >/= 20 mm with conventional techniques and >/= 10 mm with spiral CT, based on Response Evaluation Criteria in Solid Tumors (RECIST)
Lesions that are considered nonmeasurable include:
- Bone lesions
- Ascites and pleural/pericardial effusions
- Lymphangitis cutis/pulmonis
- Abdominal masses not confirmed and not followed by imaging studies
- Cystic lesions
- Tumors treated by irradiation or intra-tumor injection therapy without progression in that area or measurable disease outside that area
6. ECOG performance status 7. At least 4 weeks and recovery from effects of prior surgery or other therapy, including immunotherapy, radiotherapy, or cytokine, biologic, or vaccine therapy
8. Adequate organ function, defined as:
a. Absolute neutrophil count (ANC) = 1500/mm3
b. Platelet count = 100,000/mm3
c. Hemoglobin = 11 g/dL without need for hematopoietic growth factor or transfusion support
d. Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance = 50 mL/min
e. Serum bilirubin = 1.5 x ULN
f. Aspartate aminotransferase (AST) = 2.5 x ULN
g. Alanine aminotransferase (ALT) = 2.5 x ULN
h. Alkaline phosphatase = 2.5 x ULN
i. Serum albumin = 3.0 g/dL
j. Prothrombin time (PT) = 1.5 x ULN (or international normalized ratio [INR] = 1.3)
k. Partial thromboplastin time (PTT) = 1.5 x ULN
9. At least 18 years of age
10. Venous access adequate to maintain a 5-day continuous intravenous infusion
11. Intellectual, emotional, and physical ability to maintain an ambulatory infusion pump.
12. In women of childbearing potential (that is, all women except for those who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization), a negative serum pregnancy test within 7 days prior to randomization. 13. In subjects of childbearing potential (that is, all men and all women excluding women who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization), agreement to use a highly effective form of contraception (ie, one that has a failure rate of < 1%) throughout the treatment phase of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior cytotoxic chemotherapy, including regional perfusion, or prior Genasense treatment
2. Need for other anticancer treatment (such as chemotherapy, radiation, or biologic or investigational therapies) while receiving protocol therapy in this study
3. Primary ocular or mucosal melanoma
4. Bone-only metastatic disease
5. History or presence of brain metastasis or leptomeningeal disease
6. History of second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 or more years)
7. Significant medical disease other than cancer, such as: uncontrolled congestive heart failure; active symptoms of coronary artery disease (defined as uncontrolled arrhythmias or recurrent chest pain despite prophylactic medication); New York Heart Association Class III or IV disease; cardiovascular signs and symptoms >/= Grade 2 by common toxicity criteria (CTC) during the 4-week period prior to initiation of protocol therapy; uncontrolled seizure disorder; history of chronic hepatitis or cirrhosis; active infection; uncontrolled diabetes mellitus; requirement for chronic corticosteroid treatment with an average dose >/= 20 mg/day of prednisone (or equivalent); requirement for concurrent immunosuppressive drug(s); active autoimmune disease
8. Organ allograft
9. Known human immunodeficiency virus infection
10. Pregnancy or lactation
11. Known hypersensitivity to dacarbazine or phosphorothioate-containing oligonucleotides
12. Use of any experimental therapy within 3 weeks prior to screening evaluations.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to compare progression-free survival and overall survival in the dacarbazine plus Genasense treatment group and the dacarbazine plus placebo treatment group.;Secondary Objective: The secondary objectives of this study are to compare the 2 treatment groups with respect to the percentages of subjects with response and durable response, duration of response, and the safety of the 2 treatment regimens.;Primary end point(s): The primary endpoints are progression-free survival and overall survival.

Secondary Outcome Measures

Name	Time	Method

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