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A Randomized Phase II Trial of ATN-224 in Combination With Temozolomide or Temozolomide Followed by ATN-224 in Patients With Advanced Melanoma

Phase 2
18 Years
Open (Enrolling)

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Trial Information

A Randomized Phase II Trial of ATN-224 in Combination With Temozolomide or Temozolomide Followed by ATN-224 in Patients With Advanced Melanoma

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

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.

Inclusion 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)


- 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

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

24-week progression-free survival of the combination of temozolomide with ATN 224 and of temozolomide alone

Principal Investigator

Gilad Gordon, MD

Investigator Role:

Study Director


United States: Food and Drug Administration

Study ID:




Start Date:

September 2006

Completion Date:

September 2008

Related Keywords:

  • Melanoma
  • ATN-224
  • Temozolomide
  • Combination
  • Sequential
  • Anti-angiogenic
  • Copper
  • Melanoma



Arizona Cancer Center Tucson, Arizona  85724
Florida Cancer Specialists Fort Myers, Florida  33901
Mary Crowley Medical Research Center Dallas, Texas  75246
University of Colorado Health Science Center Aurora, Colorado  80010-0510
Hematology and Oncology Specialists, LLC New Orleans, Louisiana  70115
Cancer Center of the Carolinas Greenville, South Carolina  29615
Center for Cancer and Blood Disorders Bethesda, Maryland  20817
Billings Clinic Billings, Montana  59107-7000
Chattanooga Oncology and Hematology Associates Chattanooga, Tennessee  37404
Tennessee Oncology Nashville, Tennessee  37203
Oncology Hematology Care Cincinnati, Ohio  45242
The Angeles Clinic Santa Monica, California  90404
Pacific Oncology and Hematology Encinitas, California  92024
Hematology - Oncology Group of Orange, Inc. Orange, California  92868
UCI Chao Family Comprehensive Cancer Center Orange, California  92868
The Harry and Jeanette Weinberg Cancer Institute at Franklin Square Baltimore, Maryland  21237
Mountainside Hospital Cancer Center - The Melanoma Center Montclair, New Jersey  07042