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A Phase I/II Study of Sunitinib and Dacarbazine in Patients With Metastatic Melanoma

Phase 1/Phase 2
18 Years
Not Enrolling

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Trial Information

A Phase I/II Study of Sunitinib and Dacarbazine in Patients With Metastatic Melanoma

This is a combination Phase I/II design that explores the toxicity and activity of a
combination of sunitinib and Dacarbazine (DTIC) for metastatic melanoma. Screening tests
(pre-study) will consist of a history, physical, CBC, CMP, EKG, pregnancy test for women of
childbearing age, amylase (blood test for diagnoses of pancreatitis or other pancreatic
diseases), staging CT, and PK. Also, on day 1, these tests will be repeated - a history,
physical, toxicity assessment, CBC, and amylase test. Re-staging tests will be performed
after 2 complete cycles and follow up as indicated clinically.

The initial Phase I part of this trial will consist of a dose escalation of sunitinib while
keeping the DTIC dose constant. Sunitinib will be given 2 weeks on and 1 week off with DTIC
given once every 21 days for one cycle. If no DLT is seen, the maximum tolerated sunitinib
dose will be the suggested as the Phase II trial dose.

Tumor response will be measured after 2 complete cycles. Subsequently, during Phase II the
trial will enroll more patients; if less than 2 responses are seen, patients will not be
enrolled any further, and the study will be considered negative for activity. But, if a
clinical response is seen, more patients will be enrolled at the Phase II dose.

Inclusion Criteria:

- Histologically or cytologically documented Stage IV or unresectable Stage III

- Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to
NCI CTCAE Version 3.0 grade less than or equal to 1

- Adequate organ function as defined by the following criteria:

1. Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase
[SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase
[SGPT]) less than or equal to 2.5 x local laboratory upper limit of normal
(ULN), or AST and ALT less than or equal to 5 x ULN if liver function
abnormalities are due to underlying malignancy

2. Total serum bilirubin less than or equal to 1.5 x ULN

3. Absolute neutrophil count (ANC) greater than or equal to 1500/mcL

4. Platelets greater than or equal to 100,000/mcL

5. Hemoglobin greater than or equal to 9.0 g/dL

6. Serum calcium less than or equal to 12.0 mg/dL

7. Serum creatinine less than or equal to 1.5 x ULN

- Patients with CNS metastasis must have had either:

1. Resected CNS metastasis without evidence of recurrence for >12 weeks

2. Brain metastasis treated by stereotactic radiosurgery without evidence of
recurrence or progression for 12 weeks

3. Multiple brain lesions treated with WBRT with stable disease off corticosteroids
for at least 12 weeks prior to start of therapy

4. Without any evidence of leptomeningeal disease

5. Patients must be neurologically intact

- May have previous adjuvant therapy with interferon, vaccines or therapy with IL-2 or

- Measurable disease by RECIST criteria

- In the phase I part of the trial patients with evaluable but not measurable disease
may be allowed with the permission of the PI

- ECOG PS 0-2

Exclusion Criteria:

- Major surgery or radiation therapy within 4 weeks of starting the study treatment.

- NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.

- History of or known carcinomatous meningitis, or evidence of symptomatic
leptomeningeal disease on screening CT or MRI scan.

- Any of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident or transient
ischemic attack, or pulmonary embolism.

- Ongoing cardiac dysrhythmias of NCI CTCAE grade greater than or equal to 2.

- QTc >470 msec on baseline EKG.

- History of active CHF or LVEF<50% at screening echocardiogram.

- Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal
medical therapy).

- Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
the normal range with medication.

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness or other active infection.

- Concurrent treatment on another clinical trial. Supportive care trials or
non-treatment trials, e.g. QOL, are allowed.

- Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg po
daily for thromboembolism prophylaxis is allowed).

- Pregnancy or breastfeeding. Female subjects must be surgically sterile or be
postmenopausal, or must agree to use effective contraception during the period of
therapy. All female subjects with reproductive potential must have a negative
pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically
sterile or must agree to use effective contraception during the period of therapy.
The definition of effective contraception will be based on the judgment of the
principal investigator or a designated associate.

- Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and
in the judgment of the investigator would make the subject inappropriate for entry
into this study.

- Patients may not have had previous treatment with a DTIC or temozolomide based
chemotherapy regimen. In the Phase II part of the trial patients may not have had
treatment with any chemotherapy regimen.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the toxicity and safety of this combination and determine the recommended Phase II dose of this combination.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Adil Daud, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

UCSF (formerly at H. Lee Moffitt Cancer Center & Research Institute)


United States: Institutional Review Board

Study ID:




Start Date:

September 2006

Completion Date:

June 2007

Related Keywords:

  • Melanoma
  • Sunitinib
  • Dacarbazine
  • Melanoma
  • Melanoma



H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida  33612