Temozolomide and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

NCT00568048 | Completed Phase 2

• 4 other identifiers: SAKK 50/07SWS-SAKK-50/07EU-20790CDR0000577499
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving temozolomide together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving temozolomide together with bevacizumab works in treating patients with stage IV melanoma that cannot be removed by surgery.

Conditions

Melanoma (Skin)

Keywords

stage IV melanoma; recurrent melanoma

Outcome Measures

Primary Outcomes (1)

• Clinical benefit number of patients with complete response [CR], partial response [PR], or stable disease) according to RECIST criteria

  at 12 weeks

Secondary Outcomes (5)

• Best overall response (CR, PR) according to RECIST criteria

  from trial treatment start until PD

• Duration of response

  time from disease stabilisation until PD

• Progression free survival

  time from trial registration until disease progression or death

• Overall survival

  time from trial registration until death

• Adverse events

  time from start trial treatment until 30 days after treatment stop. Adverse events will be assessed according to NCI CTCAE v3.0.

Study Arms (1)

Combination Therapy Temozolomide & Bevacizumab

EXPERIMENTAL

Combination therapy * Temozolomide 150 mg/m2 p.o., days 1-7, repeated every 14 days * Bevacizumab 10 mg/kg i.v., day 1, repeated every 14 days

Biological: bevacizumab; Drug: temozolomide

Interventions

bevacizumab BIOLOGICAL

10 mg/kg i.v., on day 1 of every cycle (14 days) until PD or any other event qualifying for stopping treatment

Also known as: Avastin

Combination Therapy Temozolomide & Bevacizumab

temozolomide DRUG

150 mg/m2 p.o., on days 1-7 of every cycle (14 days) until PD or any other event qualifying for stopping treatment

Also known as: Temodal

Combination Therapy Temozolomide & Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed melanoma * Unresectable stage IV disease * Mucosal and unknown primary disease allowed * Measurable disease, defined as at least one lesion that can be measured in at least one dimension as ≥ 20 mm (or as ≥ 10 mm if the CT slice thickness is ≤ 5 mm) * Measurable lesion must be outside a previously treated area * Must have 1 paraffin block of primary tumor and/or metastatic tissue available for analysis of MGMT * No ocular melanoma * No bleeding skin metastases * No CNS metastases (even if previously treated) by brain MRI PATIENT CHARACTERISTICS: * WHO performance status 0-2 * ANC ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Hemoglobin ≥ 90 g/L (transfusion allowed) * Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT and alkaline phosphatase ≤ 2.5 times ULN (5 times ULN in patients with liver metastases) * Serum creatinine \< 177 μmol/L * Proteinuria \< 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection * INR ≤ 1.5 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 12 months after completion of study treatment * No other primary tumors within the past 5 years, except adequately controlled limited basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No history or evidence of CNS disease unrelated to cancer (e.g., uncontrolled seizures) by physical/neurological examination, unless adequately treated with standard medical therapy * No frequent vomiting or any other pre-existing medical condition that would preclude swallowing and/or absorption of oral medication * No history or evidence of inherited bleeding diathesis or coagulopathy with risk of bleeding * No uncontrolled hypertension (i.e., systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \> 100 mm Hg, measured repeatedly, despite adequate treatment with at least two different antihypertensive drugs) * No clinically significant (i.e., active) cardiovascular disease, including any of the following: * Cerebrovascular accident/stroke or myocardial infarction within the past 6 months * Unstable angina * New York Heart Association (NYHA) class II or greater congestive heart failure * Serious cardiac arrhythmia (i.e., ventricular arrhythmia, high-grade atrioventricular-block) that requires medication during the study, interferes with regularity of the study treatment, or is uncontrolled by medication * No serious non-healing wound, active peptic ulcer, or non-healing bone fracture * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No significant traumatic injury within the past 30 days * No uncontrolled active infection * No known HIV infection * No known hypersensitivity to any of the study drugs or excipients * No evidence of any other disease, metabolic or psychological dysfunction, psychiatric disorder, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, or that may affect patient compliance with study routines, or places the patient at high risk from treatment-related complications PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior adjuvant cytokine therapy (e.g., interleukin, interferon) or vaccine therapy and recovered * Prior vaccine therapy for stage IV disease allowed * Prior perfusion therapy (limb and liver) for loco-regional disease allowed * No prior chemotherapy for metastatic disease * No prior bevacizumab or other angiogenic inhibitors * No prior radiotherapy to lesion(s) selected for measurement * More than 30 days since prior treatment in a clinical trial * More than 30 days since prior major surgery with high risk of bleeding * More than 24 hours since prior minor surgery * More than 10 days since prior and no concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes * Prophylactic use of anticoagulants is allowed (e.g., maintenance of venous catheter) * More than 10 days since prior and no concurrent acetylsalicylic acid (\> 325 mg/day) or clopidogrel (\> 75 mg/day) * No other concurrent non-steroidal anti-inflammatory drugs (NSAIDs) * No concurrent dipyridamole * No concurrent major surgery * No concurrent radiotherapy to the target lesions * No other concurrent experimental drugs or anticancer therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (1)

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Related Publications (4)

• von Moos R, Seifert B, Simcock M, Goldinger SM, Gillessen S, Ochsenbein A, Michielin O, Cathomas R, Schlappi M, Moch H, Schraml PH, Mjhic-Probst D, Mamot C, Schonewolf N, Dummer R; Swiss Group for Clinical Cancer Research (SAKK). First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07). Ann Oncol. 2012 Feb;23(2):531-6. doi: 10.1093/annonc/mdr126. Epub 2011 Apr 28.

  PMID: 21527587 RESULT

• Dummer R, Michielin O, Seifert B, et al.: First-line temozolomide (TEM) combined with bevacizumab (BEV) in metastatic melanoma (MM): A multicenter phase II trial (SAKK 50/07). [Abstract] J Clin Oncol 28 (Suppl 15): A-8521, 2010.

  RESULT

• Fuerstenberger G, Boneberg E, Simcock M, et al.: Predictive and prognostic potential of angiogenic serum factors and circulating endothelial cells in metastatic melanoma patients receiving temozolamide plus bevacizumab (SAKK 50/07). [Abstract] J Clin Oncol 28 (Suppl 15): A-8585, 2010.

  RESULT

• Schraml P, von Teichman A, Mihic-Probst D, Simcock M, Ochsenbein A, Dummer R, Michielin O, Seifert B, Schlappi M, Moch H, von Moos R. Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07. Oncol Rep. 2012 Aug;28(2):654-8. doi: 10.3892/or.2012.1826. Epub 2012 May 18.

  PMID: 22614944 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

Bevacizumab; Temozolomide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Roger von Moos, MD

  Kantonsspital Graubuenden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2007
• First Posted: December 5, 2007
• Study Start: December 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: October 1, 2011
• Last Updated: April 10, 2013

Record last verified: 2013-04

Locations

CH (1)