Randomized Trial of ATN-224 and Temozolomide in Advanced Melanoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2007 by Attenuon.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Attenuon
ClinicalTrials.gov Identifier:
NCT00383851
First received: October 2, 2006
Last updated: December 4, 2007
Last verified: December 2007
  Purpose

This is a multicenter, randomized, phase II study to evaluate the safety and efficacy of oral ATN-224 plus temozolomide in patients with advanced melanoma. Patients will be randomized (1:1) between temozolomide and ATN-224 and temozolomide followed by ATN-224. Patients assigned to the sequential treatment group will receive temozolomide until progression of disease is documented and then receive ATN-224 as a single agent until documentation of progression of disease using the last tumor assessment on temozolomide therapy as the baseline assessment.


Condition Intervention Phase
Melanoma
Drug: ATN-224
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of ATN-224 in Combination With Temozolomide or Temozolomide Followed by ATN-224 in Patients With Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by Attenuon:

Primary Outcome Measures:
  • 24-week progression-free survival of the combination of temozolomide with ATN 224 and of temozolomide alone
  • Evaluate the safety of ATN-224 in combination with or following temozolomide

Secondary Outcome Measures:
  • Response rate (complete and partial response), rate of stable disease for ≥24 weeks, and progression-free survival for treatment with the combination of ATN 224 and temozolomide
  • Response rate (complete and partial response), rate of stable disease for ≥24 weeks, and progression-free survival for treatment with temozolomide alone
  • Response rate (complete and partial response), rate of stable disease for ≥24 weeks, and progression-free survival for treatment with ATN 224 alone after progression of disease on temozolomide
  • Time to treatment failure by progression of disease or death for patients receiving ATN 224 plus temozolomide and for patients receiving temozolomide followed by ATN 224
  • Explore blood and tumor biomarkers with the potential to correlate with activity

Estimated Enrollment: 60
Study Start Date: September 2006
Estimated Study Completion Date: September 2008
Detailed Description:

According to the National Cancer Institute PDQ database, advanced melanoma is refractory to most standard systemic therapy, and all newly diagnosed patients should be considered candidates for clinical trials. Although advanced melanoma is relatively resistant to therapy, several biologic response modifiers and cytotoxic agents have been reported to produce objective responses. Once melanoma is metastatic, treatments are palliative rather than curative. In spite of many attempts at multimodality therapy, the prognosis in this disease remains poor. Further agents are needed if progress is to be made with melanoma treatment.

ATN-224 is an orally active, small molecule that has been shown in cellular and animal models to be antiangiogenic and to have activity against melanoma cell lines. Clinical studies with a similar agent (ammonium tetrathiomolybdate) indicate that the agent can be administered continuously on a daily basis for years in some patients. ATN-224 has the potential to affect the progression of melanoma by mechanisms that include both antiangiogenic and antitumor pathways. Temozolomide, a commonly used agent for melanoma, also has a tolerable profile.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • Patients with histologically confirmed, advanced cutaneous melanoma. Advanced melanoma is defined as locally advanced disease that is not amenable to surgery or radiation therapy and metastatic disease. Patients may have had adjuvant treatment for prior early disease as long as it was given at least 6 months before the first dose of study medication, and the treatment did not contain temozolomide or dacarbazine. Previous treatment for advanced disease is acceptable as long as the patient did not receive temozolomide or dacarbazine. There is no restriction on the number of prior regimens.
  • Age ≥18 years
  • Life expectancy of greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥50%; see Appendix A)
  • Patients must have adequate organ and marrow function as defined below:

    • absolute neutrophil count ≥1,500/uL
    • platelets ≥100,000/uL
    • hemoglobin ≥9 g/dL
    • total bilirubin ≤2 X institutional upper limit of normal (ULN)
    • AST(SGOT) and ALT(SGPT) ≤2 X ULN
    • creatinine clearance (measured or calculated) ≥30 mL/min

Patients are allowed to receive erythropoietin or blood transfusions before receiving their first dose of ATN-224 to bring the hemoglobin level to >9 g/dL to meet eligibility criteria.

  • Use of adequate contraception. Temozolomide has the potential to cause fetal harm. The effects of ATN 224 on the developing human fetus at the recommended therapeutic dose are unknown, but antiangiogenic agents are known to be teratogenic. For these reasons women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal and/or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation through the follow up visit 28 days after the last dose of ATN 224 or temozolomide.
  • Willingness to forgo taking copper- or zinc-containing vitamins or supplements
  • Ability to understand and the willingness to sign a written informed consent document
  • Uveal (ocular) melanoma
  • Brain metastasis that has not been treated and remained stable for at least 4 weeks (In other words, patients are eligible if they have no metastases or if brain metastases have been treated and remain stable for at least 4 weeks)
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ATN-224 or omeprazole
  • History of malabsorption syndromes or other gastrointestinal disorders that may affect ATN-224 or temozolomide absorption, including bowel obstruction, celiac disease, sprue, cystic fibrosis
  • Ineligible to receive either temozolomide (Temodar®), omeprazole (Prilosec®), lansoprazole (Prevacid®), pantoprazole (Protonix®), or ranitidine (Zantac®)
  • Inability to swallow study medication capsules
  • Other serious medical or psychiatric illness preventing informed consent or with the potential to interfere with assessment of safety or efficacy of ATN-224 treatment
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients known to be positive for HIV or infectious hepatitis type A, B or C
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00383851

Locations
United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, California
Pacific Oncology and Hematology
Encinitas, California, United States, 92024
Hematology - Oncology Group of Orange, Inc.
Orange, California, United States, 92868
UCI Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
The Angeles Clinic
Santa Monica, California, United States, 90404
United States, Colorado
University of Colorado Health Science Center
Denver, Colorado, United States, 80262
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Louisiana
Hematology and Oncology Specialists, LLC
Metairie, Louisiana, United States, 70006
United States, Maryland
The Harry and Jeanette Weinberg Cancer Institute at Franklin Square
Baltimore, Maryland, United States, 21237
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Montana
Billings Clinic
Billings, Montana, United States, 59101
United States, New Jersey
Mountainside Hospital Cancer Center - The Melanoma Center
Montclair, New Jersey, United States, 07042
United States, Ohio
Oncology Hematology Care
Cincinati, Ohio, United States, 45242
United States, South Carolina
Cancer Center of the Carolinas
Greenville, South Carolina, United States, 29605
United States, Tennessee
Chattanooga Oncology and Hematology Associates
Chattanooga, Tennessee, United States
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Attenuon
Investigators
Study Director: Gilad Gordon, MD
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00383851     History of Changes
Other Study ID Numbers: ATN-224-008
Study First Received: October 2, 2006
Last Updated: December 4, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by Attenuon:
ATN-224
Temozolomide
Combination
Sequential
Anti-angiogenic
Copper

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Temozolomide
Dacarbazine
Tetrathiomolybdate
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Chelating Agents
Sequestering Agents
Enzyme Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on September 29, 2014