Temozolomide, Thalidomide, and Lomustine (TTL) in Melanoma Patients

NCT00527657 | Completed Phase 1

• 2 other identifiers: 2004-0595NCI-2012-01587
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest safe dose of lomustine (CCNU, CeeNUTM) that can be given with temozolomide (TemodarTM) and thalidomide (ThalomidTM) in the treatment of metastatic melanoma that has spread to the brain. The safety and effectiveness of this combination therapy will also be studied.

Conditions

Brain Neoplasms; Melanoma

Keywords

Brain Neoplasms; Melanoma; Metastatic Melanoma; Brain Metastasis; Temozolomide; Temodar; Thalidomide; Thalomid; Lomustine; CCNU; CeeNU

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  1 cycle (8 weeks) of therapy

Secondary Outcomes (1)

• Objective (CR+PR) response rate at the MTD

  1 cycle (8 weeks) of therapy

Study Arms (1)

Lomustine + Temozolomide + Thalidomide

EXPERIMENTAL

Lomustine starting dose 30 mg/m\^2 by mouth daily on Day 1 and 29. Temozolomide 75 mg/m\^2 by mouth daily on Days 1 to 42. Thalidomide 200 mg/m\^2 by mouth daily.

Drug: Lomustine; Drug: Temozolomide; Drug: Thalidomide

Interventions

Lomustine DRUG

Starting dose 30 mg/m\^2 by mouth daily on Day 1 and 29.

Also known as: CCNU, CeeNU

Lomustine + Temozolomide + Thalidomide

Temozolomide DRUG

75 mg/m\^2 by mouth daily on Days 1 to 42.

Also known as: Temodar

Lomustine + Temozolomide + Thalidomide

Thalidomide DRUG

200 mg/m\^2 by mouth daily.

Also known as: Thalomid

Lomustine + Temozolomide + Thalidomide

Eligibility Criteria

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

You may qualify if:

• Histologic Documentation: Histologic or cytologic diagnosis of distant metastatic melanoma and clinical evidence of brain metastasis.
• Pts must have brain lesions of =/\> 1.0cm longest dimension by MRI or spiral CT, if MRI not feasible or \> 0.5cm by MRI with 3D images. Pts with/without extracranial disease are eligible. Measurable extracranial disease is not required. Lesions that are considered non-measurable include: \<1.0 cm by MRI or Spiral CT, Bone lesions, Leptomeningeal disease, Ascites, Pleural/pericardial effusion, Lymphangitis cutis/pulmonis, Abdominal masses that are not confirmed and followed by imaging techniques, Cystic lesions, lesions that are in a previously irradiated area, unless new growth can be documented.
• Age \>/= 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1
• No more than 1 prior chemotherapy regimen and no prior chemotherapy for brain metastases. No prior treatment with continuous daily dose of temozolomide; prior immunotherapy and surgical resection are permitted. Patients with prior history of whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) are permitted providing that there is measurable lesion with documented growth post radiation or new disease.
• (#5 continued) Progression of lesions treated with WBRT must be shown by 2 post treatment brain imaging at least 3 weeks apart. Progression of disease is also considered when the patient had increase of lesions as per MRI of brain obtained 4 weeks or more after WBRT completed when compared to baseline MRI obtained less than 1 week prior to start of radiation. Lesions treated with SRS must have responded and then progressed.
• The following time periods must have elapsed since prior therapy: 3 weeks since surgical resection or stereotactic radiosurgery; 4weeks since prior whole brain radiation therapy; 6 weeks since prior nitrosureas or mitomycin C. Biologic agents used as adjuvants and vaccines or cellular therapies will not require 4-week wash out period if the patient meets all eligibility criteria.
• No frequent vomiting and/or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction).
• No other concurrent chemotherapy/immunotherapy/radiotherapy.
• No history of active angina or myocardial infarction within 6 months. No history of significant ventricular arrythmia or uncontrolled arrythmia or bradycardia. The study participants must have resting heart rate of 48 or greater (.e.i - to receive Thalidomide).
• No prior history of deep vein thrombosis (DVT) or pulmonary embolism (PE).
• No known HIV disease. Patients with a history of intravenous drug abuse or any other behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Because peripheral neuropathies are a common toxicity of antiviral therapy and of viral infection in HIV patients, as well as a common significant toxicity with thalidomide, patients who test positive or who are known to be infected are not eligible. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.
• No pre-existing neuropathy that is \>/= grade 2, including uncontrolled seizures.
• No expected need for radiotherapy to brain or any extracranial metastatic site during the period of participation in the study.
• Patients may not be taking Coumadin, warfarin or heparin products or their derivatives.

You may not qualify if:

• Presence of any ongoing toxic effect from prior treatment.
• Serious infection requiring intravenous antibiotics, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
• Concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix. Patients with previous malignancies, but which have not required anti-tumor treatment within the preceding 24 months will be allowed to enter the trial. Patients with a history of a T1a or b prostate cancer (detected incidentally at transurethral prostatectomy (TURP) and comprising less than 5% of resected tissue) may participate if the prostate-specific antigen (PSA) remained within normal limits since TURP.
• Any other medical condition or reason that, in the principal investigator's opinion, makes the patient unsuitable to participate in a clinical trial including but not limited to active bleeding, prior surgical procedures affecting absorption or gastrointestinal tract disease resulting in inability to take oral medication.
• Pregnant and lactating women.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas MD Anderson Cancer Center Official Web Site

MeSH Terms

Conditions

Brain Neoplasms; Melanoma

Interventions

Lomustine; Temozolomide; Thalidomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Nicholas E. Papadopoulos, MD

  M.D. Anderson Cancer Center

  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

Study Record Dates

• First Submitted: September 10, 2007
• First Posted: September 11, 2007
• Study Start: February 9, 2006
• Primary Completion: February 2, 2012
• Study Completion: February 2, 2012
• Last Updated: November 14, 2018

Record last verified: 2018-11

Locations

US (1)