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Trial registered on ANZCTR


Registration number
ACTRN12605000684628
Ethics application status
Approved
Date submitted
21/10/2005
Date registered
21/10/2005
Date last updated
12/02/2020
Date data sharing statement initially provided
12/02/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
A phase III randomised, placebo-controlled study of Sorafenib in repeated cycles of 21 days in combination with paclitaxel / carboplatin chemotherapy in patients with unresectable stage III or IV melanoma.
Scientific title
A phase III randomised, placebo-controlled study of Sorafenib in repeated cycles of 21 days in combination with paclitaxel / carboplatin chemotherapy in patients with unresectable stage III or IV melanoma, to compare the anti-tumor activity as measured by progression free survival.
Secondary ID [1] 203 0
Bayer Australia Ltd: 11718 Raf Kinase Melanoma Study
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable stage III or IV melanoma. 832 0
Condition category
Condition code
Cancer 899 899 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 732 0
Treatment: Drugs
Comparator / control treatment
Paclitaxel 225 mg/m2 intravenous and carboplatin AUC 6 dose dependent on patient's weight. Duration 21 day cycles, up to 10 cycles depending on patient response
Control group
Placebo

Outcomes
Primary outcome [1] 1165 0
The primary objective is to evaluate progression free survival between subjects treated with sorafenib versus placebo in combination with paclitaxel and carboplatin.
Timepoint [1] 1165 0
12 months
Secondary outcome [1] 2133 0
To evaluate overall survival between subjects treated with sorafenib versus placebo in combination with paclitaxel and carboplatin.
Timepoint [1] 2133 0
30 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sorafenib and placebo will be identical in appearance in order to preserve blinding. In order to maintain this blind, study medication (sorafenib or matching placebo) will be labeled with a unique Bottle number, which will be assigned to a subject through the telephone using an interactive voice recognition system (IVRS).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation list.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/05/2005
Actual
26/05/2005
Date of last participant enrolment
Anticipated
Actual
12/05/2006
Date of last data collection
Anticipated
Actual
9/01/2009
Sample size
Target
250
Accrual to date
Final
272
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 990 0
Self funded/Unfunded
Name [1] 990 0
Bayer Australia Ltd
Country [1] 990 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Bayer Australia Ltd
Address
875 Pacific Highway Pymble NSW 2073
Country
Australia
Secondary sponsor category [1] 854 0
None
Name [1] 854 0
none
Address [1] 854 0
Country [1] 854 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305347 0
Newcastle Mater Hospital Human Research Ethics Committee
Ethics committee address [1] 305347 0
Ethics committee country [1] 305347 0
Australia
Date submitted for ethics approval [1] 305347 0
Approval date [1] 305347 0
09/03/2005
Ethics approval number [1] 305347 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35460 0
Address 35460 0
Country 35460 0
Phone 35460 0
Fax 35460 0
Email 35460 0
Contact person for public queries
Name 9921 0
Clinical Research Manager
Address 9921 0
Bayer Australia Limited
PO Box 903
Pymble NSW 2073
Country 9921 0
Australia
Phone 9921 0
+61 2 93916140
Fax 9921 0
Email 9921 0
@bayerhealthcare.com
Contact person for scientific queries
Name 849 0
Medical Services Manager
Address 849 0
Bayer Australia Limited
PO Box 903
Pymble NSW 2073
Country 849 0
Australia
Phone 849 0
+61 2 93916147
Fax 849 0
Email 849 0
@bayerhealthcare.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.