Evaluate Safety/Tolerability Intra-Arterial Temozolomide in Patients w/Extremity Melanoma by Isolated Limb Infusion

NCT01127594 | Completed Phase 1

• 1 other identifier: Pro00020406
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine the safety profile of intra-arterial temozolomide administration during Isolated Limb Infusion (ILI) by defining the dose limiting toxicities associated with this treatment. This study also aims to determine the maximum tolerated dose of intra-arterial administration of temozolomide during ILI that will be used in a phase II trial.

Conditions

Melanoma

Keywords

Melanoma

Outcome Measures

Primary Outcomes (1)

• Safety Profile of intra-arterial temozolomide and maximum tolerated dose of temozolomide

  To determine the safety profile of intra-arterial temozolomide administration during Isolated Limb Infusion (ILI) by defining the dose limiting (DLT) and non dose limiting toxicities associated with this treatment. To determine the maximum tolerated dose (MTD) for intra-arterial administration of temozolomide during ILI that will be used in a phase II efficacy trial.

  12 Weeks

Secondary Outcomes (1)

• To define tumor response in field in patients treated with temozolomide

  Until disease progression or death

Interventions

Temozolomide DRUG

Dose level selection will proceed according to the modified Accelerated Titration Design. The starting dose will be TMZ 200mg/m2 x 0.09 BSA for the upper extremity and 200mg/m2 x 0.18 BSA for the lower extremity. We will enroll one-patient cohorts with dose doubling between cohorts until 1st occurrence of a ≥ CTC (Common Terminology Criteria) grade 2 adverse event. At that time, the present cohort and all future cohorts will be extended to enroll 3 to 6 patients.

Also known as: Temodar

Eligibility Criteria

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

You may qualify if:

• Patient must have undergone a previous Melphalan based regional therapy for which they did not respond optimally and present with persistent, progressive, or recurrent disease.
• Patient must be 18 years of age or older.
• Patient must have an ECOG status of 0-1.
• Patient must have histologically proven primary or recurrent extremity melanoma, stage IIIB, IIIC, or IV
• Patients with Stage IIIC disease must either have had regional lymph nodes previously removed or will have them removed at the time of regional treatment.
• Patients with Stage IV disease must have had all distant disease resected at least 30 days prior to regional treatment.
• Disease to be treated by ILI must be distal to the planned site of tourniquet placement
• Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the RECIST criteria.
• Patient must have adequate bone marrow, liver and renal function
• Patient must have a palpable femoral/radial pulse in the affected extremity.
• Recovery from relevant toxicity prior to first study drug administration.
• Patients must have a life expectancy of \> 6 months.
• Ability to read and understand English and the ability to complete paper +/- electronic survey assessments.

You may not qualify if:

• Cardiac disease: Congestive heart failure \> class II NYHA.
• Known brain metastasis.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Active clinically serious infection \> CTCAE Grade 2.
• Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of administration of TMZ
• Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of administration of TMZ.
• Serious non-healing wound, ulcer, or bone fracture.
• Major surgery or significant traumatic injury within 30 days of ILI.
• Evidence or history of bleeding diathesis or coagulopathy.
• Antineoplastic therapy, radiotherapy, or any other investigational drug within 30 days prior to first study drug administration.
• Patients with symptoms or signs of vascular insufficiency. Specifically, patients with any history of blood clots or lifestyle altering ischemic peripheral vascular disease will be excluded.
• History of allergic reactions and/or hypersensitivity to TMZ.
• Psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance.

Sponsors & Collaborators

• Douglas Tyler: lead
• Merck Sharp & Dohme LLC: collaborator
• Duke University: collaborator
• M.D. Anderson Cancer Center: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator

Study Sites (3)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Douglas S Tyler, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgical Oncology

Study Record Dates

• First Submitted: May 19, 2010
• First Posted: May 21, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: June 1, 2014
• Last Updated: March 9, 2015

Record last verified: 2015-03

Locations

US (3)