Temodar and Sutent as Therapy for Melanoma

NCT00304200 | Terminated Phase 1 DMC

• 1 other identifier: Temodar/Sutent
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the safety and appropriate dose of the combination of Temodar and Sutent as first-line therapy for patients with metastatic malignant melanoma (Phase 1). Once the safety and appropriate dose is determined, additional patients will be studied at that dose to determine if there is clinical benefit as determined by the primary end-point of progression-free survival (PFS) at 6 months and additional secondary endpoints (Phase II).

Conditions

Metastatic Malignant Melanoma

Keywords

Metastatic Malignant Melanoma

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of this combination

  March 2006 through October 2007

• Determine the Maximum Tolerated Dose (MTD) of this combination

  March 2006 through October 2007

Secondary Outcomes (6)

• Progression-free survival (PFS) at 6 months

  March 2006 through October 2007

• Progression-free survival (PFS)

  March 2006 through October 2007

• Overall survival (OS)

  October 2006 through January 2009

• Objective Response Rate (RR)in patients with measurable lesions

  March 2006 through October 2007

• Duration of Objective Response in patients with measurable lesions

  March 2006 through October 2007

Study Arms (1)

Single arm, Open Label

EXPERIMENTAL

Single arm, Open Label Temodar and Sutent

Drug: Temozolomide and SU11248

Interventions

Temozolomide and SU11248 DRUG

First Cohort: Temozolomide 100 mg/m2 orally week 1 and week 3 of a 28-day cycle; SU11248, 25 mg/day orally on weeks 2, 3, and 4 or a 28 day cycle.

Also known as: Temozolomide is also known as Temodar, SU11248 is also known as Sutent

Single arm, Open Label

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed, (surgically incurable or unresectable)stage IV metastatic malignant melanoma.
• Patients must not have received any prior cytokine or chemotherapy for stage IV disease.
• ECOG performance status of 0-1.
• Age greater than or equal to 18 years.
• Adequate hematologic, renal and liver function as defined by laboratory values performed within 28 days prior to initiation of dosing.
• Absolute neutrophil count (ANC) greater than or equal to 1500/uL
• Platelet count greater than or equal to 100,000/uL
• Hemoglobin greater than or equal to 10.0 g/dL
• Serum creatinine ≤ 1.5 upper limit of laboratory normal
• Total serum bilirubin less than or equal to1.5 times upper limit of laboratory normal
• LDH less than or equal to 2 times upper limit of laboratory normal
• Serum aspartate transaminase (ASAT/SGOT) or serum alanine transaminase (ALAT/SGPT) ≤ 2.5 times upper limit of laboratory normal, and ≤ 5 times upper limit of laboratory normal in cases of liver metastasis
• Patients must have recovered from effects of major surgery.
• Women of childbearing potential should be using an effective method of contraception. Women of childbearing potential must have a negative urine or serum pregnancy test up to 28 days prior to commencement of dosing and be practicing medically approved contraceptive precautions for at least 6 months after completion of treatment as directed by their physician.
• Men should use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician.

You may not qualify if:

• Major surgery or radiation therapy within 4 weeks of starting the study treatment.
• Evidence of brain metastases.
• NCI CTCAE Version 3.0 grade 3 hemorrhage within 4 weeks of starting the study treatment.
• History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan.
• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade equal to or greater than 2.
• Prolonged QTc interval on baseline EKG.
• Uncontrolled hypertension (\>150/100 mm Hg despite optimal medical therapy).
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
• Known active infection.
• Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
• Treatment with drugs with dysrhythmic potential including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, and/or indapamide.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
• Frequent vomiting or medical condition which could interfere with oral medication intake (e.g. partial bowel obstruction).
• Previous cancer (unless a DRS interval of at least 5 years) or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Northern California Melanoma Center: lead
• Pfizer: collaborator
• Schering-Plough: collaborator

Study Sites (1)

Northern California Melanoma Center

San Francisco, California, 94109, United States

Location

Related Publications (7)

• Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, Dreno B, Henz M, Schadendorf D, Kapp A, Weiss J, Fraass U, Statkevich P, Muller M, Thatcher N. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000 Jan;18(1):158-66. doi: 10.1200/JCO.2000.18.1.158.

  PMID: 10623706 BACKGROUND

• Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005 Feb 10;23(5):1011-27. doi: 10.1200/JCO.2005.06.081. Epub 2004 Dec 7.

  PMID: 15585754 BACKGROUND

• Lev DC, Ruiz M, Mills L, McGary EC, Price JE, Bar-Eli M. Dacarbazine causes transcriptional up-regulation of interleukin 8 and vascular endothelial growth factor in melanoma cells: a possible escape mechanism from chemotherapy. Mol Cancer Ther. 2003 Aug;2(8):753-63.

  PMID: 12939465 BACKGROUND

• George D. Targeting PDGF receptors in cancer--rationales and proof of concept clinical trials. Adv Exp Med Biol. 2003;532:141-51. doi: 10.1007/978-1-4615-0081-0_12.

  PMID: 12908555 BACKGROUND

• Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003 May;111(9):1287-95. doi: 10.1172/JCI17929.

  PMID: 12727920 BACKGROUND

• Erber R, Thurnher A, Katsen AD, Groth G, Kerger H, Hammes HP, Menger MD, Ullrich A, Vajkoczy P. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 2004 Feb;18(2):338-40. doi: 10.1096/fj.03-0271fje. Epub 2003 Dec 4.

  PMID: 14657001 BACKGROUND

• Pietras K, Hanahan D. A multitargeted, metronomic, and maximum-tolerated dose "chemo-switch" regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol. 2005 Feb 10;23(5):939-52. doi: 10.1200/JCO.2005.07.093. Epub 2004 Nov 22.

  PMID: 15557593 BACKGROUND

MeSH Terms

Conditions

Melanoma

Interventions

Temozolomide; Sunitinib

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Lynn E. Spitler, MD

  Northern California Melanoma Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 12, 2006
• First Posted: March 17, 2006
• Study Start: March 1, 2006
• Primary Completion: October 1, 2007
• Study Completion: January 1, 2009
• Last Updated: February 5, 2009

Record last verified: 2009-02

Locations

US (1)