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Randomized Trial of ATN-224 and Temozolomide in Advanced Melanoma

Information source: Attenuon
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Melanoma

Intervention: ATN-224 (Drug); Temozolomide (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Attenuon

Official(s) and/or principal investigator(s):
Gilad Gordon, MD, Study Director

Summary

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

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:

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

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Arizona Cancer Center, Tucson, Arizona 85724, United States

Pacific Oncology and Hematology, Encinitas, California 92024, United States

Hematology - Oncology Group of Orange, Inc., Orange, California 92868, United States

UCI Chao Family Comprehensive Cancer Center, Orange, California 92868, United States

The Angeles Clinic, Santa Monica, California 90404, United States

University of Colorado Health Science Center, Denver, Colorado 80262, United States

Florida Cancer Specialists, Fort Myers, Florida 33901, United States

Hematology and Oncology Specialists, LLC, Metairie, Louisiana 70006, United States

The Harry and Jeanette Weinberg Cancer Institute at Franklin Square, Baltimore, Maryland 21237, United States

Center for Cancer and Blood Disorders, Bethesda, Maryland 20817, United States

Billings Clinic, Billings, Montana 59101, United States

Mountainside Hospital Cancer Center - The Melanoma Center, Montclair, New Jersey 07042, United States

Oncology Hematology Care, Cincinati, Ohio 45242, United States

Cancer Center of the Carolinas, Greenville, South Carolina 29605, United States

Chattanooga Oncology and Hematology Associates, Chattanooga, Tennessee, United States

Tennessee Oncology, Nashville, Tennessee 37203, United States

Mary Crowley Medical Research Center, Dallas, Texas 75246, United States

Additional Information

Starting date: September 2006
Last updated: December 4, 2007

Page last updated: August 20, 2015

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