Pilot Trial of "Chemo-Switch" Regimen to Treat Advanced Melanoma

Phase II Pilot Trial of "Chemo-Switch" Regimen of Biochemotherapy Followed by Daily Low-Dose Temozolomide Plus Sorafenib in Advanced Melanoma

This research study is testing the "chemo-switch" strategy in melanoma, using biochemotherapy initially to shrink tumors and then switching to daily low-dose chemotherapy (temozolomide) together with sorafenib. The purpose of this study is to find out what effects (good and bad) biochemotherapy followed by temozolomide plus sorafenib have on melanoma.

Study Overview

• Status: Terminated
• Conditions: Melanoma
• Intervention / Treatment: Drug: Concurrent decrescendo biochemotherapy regimen; Drug: Low-dose Temozolomide plus Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must have histologically or cytologically confirmed melanoma that is locally advanced or metastatic. Cutaneous, mucosal, ocular, and unknown primary melanoma are all eligible.
• Must have measurable disease, defined by RECIST as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20mm with conventional techniques or >10mm with spiral CT scan.
• May have received prior radiation therapy to one or more non-index lesions (prior radiation to an index lesion is allowable only if progression of the irradiated lesion is demonstrated, with progression defined as an increase of 20% or more in the largest diameter) and/or one prior vaccine therapy for metastatic disease. Prior adjuvant therapy with IFN alpha-2b, vaccine, and/or granulocyte-macrophage colony-stimulating factor (GM-CSF) is permitted. At least 4 weks must have elapsed since the completion of any prior therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients must have normal organ and marrow function as defined below:
• leukocytes >3,000/uL (microliters)
• absolute neutrophil count >1,500/uL
• platelets >100,000/uL
• total bilirubin <2.0mg/dL
• AST (Aspartate transaminase)(SGOT)/ALT (Alanine transaminase)(SGPT) <2.5 X institutional upper limit of normal
• creatinine <1.8mg/dL
• If >50 years of age with one or more cardiac risk factors, must demonstrate normal exercise stress test, stress thallium test, or comparable cardiac ischemia evaluation.
• Must be at least 2 weeks out from major surgery and be free of any active infection requiring antibiotics.
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Women must demonstrate a negative pregnancy test prior to initiation of protocol therapy.
• Ability to understand and the willingness to sign a written informed consent form.

Exclusion Criteria:

• Prior chemotherapy, cytokine therapy (including IL-2 or IFN alpha), or antibody therapy for metastatic disease. Prior vaccine therapy is permitted.
• May not be currently receiving any other antineoplastic treatments, including chemotherapy, biologic response modifiers, radiation, vaccine, or investigational agents.
• History of brain metastases.
• Autoimmune disorders that could result in life-threatening complications in the setting of IFN alpha and IL-2 treatment.
• History of sensitivity to E. coli-derived products.
• Concurrent use of corticosteroids or any medical condition likely to require the use of systemic corticosteroids.
• A seizure disorder currently requiring anti-epileptic medication.
• Uncontrolled intercurrent illness including, but not limited to, hypertension, active infection requiring antibiotic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Evidence of bleeding diathesis.
• Currently on therapeutic anticoagulation. Prophylactic anticoagulation (such as low-dose warfarin) of venous or arterial access devices is allowed provided the PT, PTT (Partial Thromboplastin Time), and international normalized ratio (INR) are normal.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: "Chemo-Switch" Regimen

Drug: Concurrent decrescendo biochemotherapy regimen; Temozolomide: 200mg/m^2, daily, PO, days 1-4; Vinblastine: 1.5mg/m^2, daily, IV, days 1-4; Cisplatin: 20mg/m^2, daily IV, days 1-4; IL (interleukin)-2: - 18 milli-International unit (MIU)/m^2, IVCI (intravenous continual infusion), day 1; 9 MIU/m^2, IVCI, day 2; 4.5 MIU/m^2, IVCI, days 3 & 4; Interferon (IFN) alpha: 5 MIU/m^2, daily, SC (subcutaneously), days 1-5; 5-day inpatient regimen, to be repeated every 21 days; Drug: Low-dose Temozolomide plus Sorafenib; Temozolomide: 75mg/m^2, PO, QD (quaque die), 6 weeks on/2 weeks off Sorafenib: 400mg, PO, BID, 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Terminated study before accrual goal, no data analysis	3 weeks, 6 weeks, 16 weeks, & 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Response Rate as Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	post-cycle 1 of low-dose temozolomide plus sorafenib, then every 3 months for up to 2 years

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Bayer

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: May 4, 2008
• First Submitted That Met QC Criteria: May 4, 2008
• First Posted (Estimate): May 7, 2008

Study Record Updates

• Last Update Posted (Estimate): January 13, 2016
• Last Update Submitted That Met QC Criteria: January 11, 2016
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Protein Kinase Inhibitors; Temozolomide; Sorafenib
• Other Study ID Numbers: 9361; SR05-888 (Other Identifier: Legacy Study ID)