None listed
Conditions
Interventions
The objectives of this study are to compare the anti-tumor activity as measured by Progression Free Survival (PFS) and tolerability of sorafenib in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in combination with placebo in subjects with unresectable Stage III or Stage IV melanoma who progressed after receiving only one prior therapy containing DTIC or TMZ.
Subjects will be randomized to one of the following treatment groups:
Group A - Sorafenib, 400 mg po, Stud
The objectives of this study are to compare the anti-tumor activity as measured by Progression Free Survival (PFS) and tolerability of sorafenib in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin in combination with placebo in subjects with unresectable Stage III or Stage IV melanoma who progressed after receiving only one prior therapy containing DTIC or TMZ. Subjects will be randomized to one of the following treatment groups: Group A - Sorafenib, 400 mg po, Study Days 2-19 + paclitaxel (225 mg/m2 iv) and carboplatin (AUC 6 iv) on Study Day 1. Group B - Placebo, Study Days 2-19 + paclitaxel (225 mg/m2 iv) and carboplatin (AUC 6 iv) on Study Day 1. Subjects will receive up to 10 cycles of carboplatin/paclitaxel until disease progression or non-tolerated toxicity. If their disease status is Stable Disease (modified RECIST Criteria) or better following 10 cycles of carboplatin/paclitaxel, subjects will continue sorafenib/placebo treatment (no rest, no interruption day 19-21) until disease progression or intolerability is documented.
Sponsors
Bayer Australia Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Histologically or cytologically confirmed unresectable (Stage III) or metastatic (Stage IV) melanoma. Measurable disease defined as at least one lesion that can be accurately and serially measured per the modified RECIST criteria. Cutaneous lesions measuring at least 1 cm will be considered measurable.ECOG Performance Status of 0 or 1.Life expectancy of at least 12 weeks.Subjects must have progressed after receiving at least one cycle of DTIC (with a minimum total dose of 850 mg/m2) or TMZ (with a minimum total dose of 750 mg/m2) containing regimen. Subjects may not have received more than one prior regimen in either the adjuvant or metastatic setting.Previous chemotherapy, biologic therapy, or radiation treatment must have been discontinued at least 4 weeks prior to study entry and subjects must have recovered from adverse events due to those agents.Signed informed consent must be obtained prior to any study specific procedures.Adequate bone marrow, liver and renal function..Subjects must not have any evidence of a bleeding diathesis.Serum creatinine less than 1.5 x ULNSerum amylase less than or equal 1.5 ULN. Lipase will be assessed in case abnormal values of amylase. Subjects with lipase less than or equal to 1.5 x ULN will be eligible.
Exclusion criteria
Primary ocular or mucosal melanoma.Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis & Ti) or any cancer curatively treated < 5 years prior to study entry.Clinically evident congestive heart failure.Cardiac arrhythmias including atrial fibrillation are excluded if not adequately controlled. Subjects on beta-blockers and digoxin must be monitored closely as sorafenib may affect metabolism of these agents.Active coronary artery disease or ischemia.Uncontrolled hypertension.Active clinically serious infections. Subjects who have received parenteral antibiotics within 4 weeks of treatment are excludedSubjects with seizure disorder requiring medication. The use of carbamazepine, phenytoin and phenobarbital (drugs that induce CYP450 3A4 activity) is prohibited as these may enhance the metabolism of sorafenib and decrease serum concentrationsHistory of or suspected HIV infection or chronic hepatitis B or C.Active CNS metastatic or meningeal tumors will be excluded. History of organ allograft or stem cell transplantation.Pregnant or breast-feeding subjects. Both men and women must use two methods of adequate barrier birth control measures from screening until at least 28 days into the active follow-up period of the study.Prior radiation therapy is allowed. Prior treatment with a Ras pathway inhibitor, or treatment with a drug which targets VEGF.Radiotherapy, except palliative radiotherapy will not be allowed during study participation.Major surgery within 4 weeks of study entry.Subjects who have received more than one prior DTIC or TMZ containing regimen in either the adjuvant or metastatic setting. Prior treatments include, additional anticancer therapy, or investigational treatment.Biological response modifiers within 3 weeks of study entry.Use of St Johns Wort and rifampicin during the study or within 3 weeks of the first dose of study entry.Substance abuse, medical, psychological or social conditions that may interfere with the subjects participation in the study or evaluation of the study results.Known or suspected allergy to the investigational agent or any agent given inassociation with this trial.Unresolved chronic toxicity.
Outcome results
None listed