Phase III randomised, placebo controlled study of sorafenib in repeated cycles of 21 days in combination with paclitaxel/carboplatin chemotherapy in subjects with unresectable stage III or stage IV melanoma
- Conditions
- unresectable, advanced Stage III or Stage IV melanoma
- Registration Number
- EUCTR2005-000941-12-GB
- Lead Sponsor
- Onyx Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
- Histologically or cytologically confirmed unresectable (Stage III) or metastatic (Stage IV) melanoma
- Male and female subjects of > =18 years of age
- 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 in the advanced or metastatic setting. Subjects may not have received more than one prior regimen in the metastatic setting. Subjects must have evidence of progressive disease prior to study entry. Subjects may have received prior immunotherapy, cytokine, biological or vaccine regimen in the adjuvant 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 as assessed by the following laboratory requirements:
- Hemoglobin > 9.0 g/dl
- Absolute neutrophil count (ANC) >1,500/mm3
- Platelet count > = 100,000/mm3
- Total bilirubin < 1.5 times the ULN
- ALT and AST < = 2.5 x ULN (5.0 x ULN for subjects with hepatic involvement with tumor)
- INR < = 1.5 or a PTT within normal limits. Subjects must not have any evidence of a bleeding diathesis. (Subjects who are on therapeutic anticoagulation with warfarin should have documentation of a normal PT/PTT prior to initiating that therapy.)
- Serum creatinine < 1.5 x ULN
- Serum amylase < = 1.5 ULN. Lipase will be assessed in case abnormal values of amylase. Subjects with lipase < = 1.5 x ULN will be eligible.
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
- 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
- Excluded medical conditions:
a. Clinically evident congestive heart failure, as defined by New York Health Association (NYHA) > class 2
b. 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
c. Active coronary artery disease or ischemia (myocardial infarction within the last 6 months prior to study entry)
d. Uncontrolled hypertension
e. Active clinically serious infections (> grade 2 NCI CTCAE Version 3.0). Subjects who have received parenteral antibiotics within 4 weeks of treatment are excluded
f. Subjects with seizure disorder requiring medication (such as anti-epileptics). 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 concentrations
g. History of or suspected HIV infection or chronic hepatitis B or C
h. Active CNS metastatic or meningeal tumors will be excluded. Patients with prior disease must be at least 3 months off definitive therapy. They must have a negative imaging study (MRI or CT) within 4 weeks of study entry (if imaging study indicates residual scarring, the lesion must be stable for at least 3 months prior to study entry)
i. History of organ allograft or stem cell transplantation
j. Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test result within 7 days prior to the first sorafenib/placebo administration. For the purposes of this study, post-menopausal >1 year without menses and females who are surgically sterilized will not be required to have pregnancy testing
k. Both men and women enrolled in this study must use at least one method of adequate barrier birth control measure from screening until at least 28 days into the active follow-up period of the study
l. Prior radiation therapy is allowed. However, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions.
- Excluded prior and concomitant therapies and medications:
a. Prior treatment with a Ras pathway inhibitor (including trastuzumab, farnesyl transferase inhibitors or MEK inhibitors), or treatment with a drug which targets VEGF will exclude subjects
b. Major surgery within 4 weeks of study entry
c. Subjects who have received more than one prior DTIC or TMZ containing regimen in the metastatic setting. Prior advanced or metastatic treatments include, additional anticancer therapy (biologics or chemotherapy), or investigational treatment in combination with DTIC or TMZ.
• Only one prior regimen is allowed in the metastat
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method