A Phase I/II Study of Dasatinib and Dacarbazine in Patients With Metastatic Melanoma
18 Years
N/A
Both
Metastatic Melanoma
Trial Information
A Phase I/II Study of Dasatinib and Dacarbazine in Patients With Metastatic Melanoma
Patient will receive Dacarbazine intravenously (IV), which means it is given through a
needle in a vein in the arm or through a venous port (if patient already has one). Dasatinib
will be given orally starting day 2 for 17 days straight (days 2 through 19) starting the
day after patient receives their first dose of Dacarbazine. The therapy will be repeated
every 21 days (21 days = 1 cycle). Patient may be given other drugs before each cycle to
help reduce side effects of the therapy. If patient experiences severe side effects, the
amount of Dacarbazine and/or Dasatinib they receive in future cycles may be decreased.
Cycle 1 day 1:
- Dacarbazine Intravenous
- Toxicity assessment - evaluation of any side effects that patient may be experiencing
- Medical history*
- Physical examination* - measure height, weight, blood pressure, pulse, breathing rate,
temperature, assessment of patient's energy and activity level (Eastern Cooperative
Group [ECOG] Performance Status)
- Blood tests (3 tablespoons) for safety tests*- Complete blood count with differential
and platelets (CBC), Comprehensive metabolic profile (CMP), & Magnesium test *(certain
tests may not need to be performed if they were performed during screening within 1
week; study doctor will tell patient if they need to have these tests redone)
Cycle 1 day 8:
- Toxicity assessment - (these will be done for the first cycle of treatment, but will be
discontinued for later cycles unless deemed necessary by study doctor)
- CBC - (1 tablespoon) (this will be done for the first cycle of treatment, but will be
discontinued for later cycles unless deemed necessary by study doctor)
- Dasatinib orally
Cycle 1 day 15:
- Toxicity assessment - (these will be done for the first cycle of treatment, but will be
discontinued for later cycles unless deemed necessary by study doctor)
- CBC - (1 tablespoon) these will be done for the first cycle of treatment, but will be
discontinued for later cycles unless deemed necessary by study doctor)
- Dasatinib orally
- Blood sample for pharmacokinetic (PK) analysis
Patient will also take Dasatinib orally as instructed days: 2, 3, 4, 5, 6, 7, 9, 10, 11, 12,
13, 14, 16, 17, 18, 19 each cycle.
Day 1 for all cycles after the first cycle:
- Dacarbazine Intravenous (IV)
- Dasatinib orally
- Medical history
- Physical examination: measure height, weight, blood pressure, pulse, breathing rate,
temperature, assessment of patient's energy and activity level (ECOG Performance
Status)
- Blood tests (2 tablespoon) for safety tests: CMP & CBC
- An electrocardiogram (EKG)
- Computed tomography (CT) scan (done every other cycle starting with cycle 2)
- Toxicity assessment
If patient decides not to continue participation in this study or is taken off the study by
their study doctor or the sponsor they will return to the clinic for one more visit.
During this visit the following procedures will be performed:
- Medical history
- Perform a physical examination: measure height, weight, blood pressure, pulse,
breathing rate, temperature, assessment of patient's energy and activity level (Eastern
Cooperative Group [ECOG] Performance Status)
- Blood tests (2 tablespoons) for safety tests: CBC & CMP
- Toxicity assessment Patient will need to take their assigned Dasatinib dose twice
daily. It may be taken with or without food.
Inclusion Criteria:
- Histologically or cytologically proven melanoma with Stage IV or unresectable stage
III disease
- Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE) Version 3.0 grade ≤1.
- Adequate organ function as defined by the following criteria:
- Serum aspartate transaminase (AST); serum glutamic oxaloacetic transaminase
(SGOT) and serum alanine transaminase (ALT); serum glutamic pyruvic transaminase
(SGPT) ≤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
- Total serum bilirubin ≤1.5 x ULN
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100,000/µL
- Hemoglobin ≥9.0 g/dL (may be transfused or erythropoietin treated)
- Serum calcium ≤12.0 mg/dL
- Serum creatinine ≤1.5 x ULN
- Patients with CNS metastasis must have had either; a) resected central nervous system
(CNS) metastasis without evidence of recurrence for >12 weeks; b) Brain metastasis
treated by stereotactic radiosurgery without evidence of recurrence or progression
for 12 weeks; Or, c) Multiple brain lesions treated with whole-brain radiation
therapy (WBRT) with stable disease off corticosteroids for at least 12 weeks prior to
start of therapy; and, d)Without any evidence of leptomeningeal disease. Patients
must be neurologically intact.
- May have previous adjuvant therapy with interferon, vaccines or therapy with IL-2 or
GM-CSF
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
is required in the Phase II portion of the trial. In the phase I part of the trial
patients with evaluable but not measurable disease may be allowed with the permission
of the Principal Investigator (PI)
- Eastern Cooperative Oncology Group (ECOG) PS 0-2
Exclusion Criteria:
- Major surgery or radiation therapy within 4 weeks of starting the study treatment.
- NCI CTCAE grade 2 or greater 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 ≥2.
- QTc >470 msec on baseline EKG.
- Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal
medical therapy).
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness or other active infection
- Ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg
orally (po) daily for thromboembolism prophylaxis is allowed).
- Pregnancy or breastfeeding. Female patients must be surgically sterile or be
postmenopausal, or must agree to use effective contraception during the period of
therapy. All female patients with reproductive potential must have a negative
pregnancy test (serum or urine) prior to enrollment. Male patients 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.
- May not have had previous treatment with a Dacarbazine (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:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Recommended Phase II Dose
Outcome Description:
To determine the maximum tolerated dose of dasatinib twice a day when given with dacarbazine. Adverse events were graded using Common Terminology Criteria for Adverse Events version 3.0. Dose-limiting toxicities are defined as any grade 4 haematological toxicity (except asymptomatic grade 4 neutropenia for =/< 7 days); prolonged grade 3 or 4 thrombocytopenia (47 days) or thrombocytopenia associated with bleeding, requiring platelet transfusion; any grade 3 or 4 nonhaematological toxicity despite optimal supportive care; any toxicity considered unacceptable by the study principal investigator.
Outcome Time Frame:
1 Year 3 Months
Safety Issue:
No
Principal Investigator
Jeffrey Weber, M.D.. Ph.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
H. Lee Moffitt Cancer Center and Research Institute
Authority:
United States: Institutional Review Board
Study ID:
MCC-15256
NCT ID:
NCT00597038
Start Date:
November 2007
Completion Date:
September 2011
Related Keywords:
- Metastatic Melanoma
- Dasatinib
- Dacarbazine
- Melanoma
Name | Location |
|---|---|
| H. Lee Moffitt Cancer Center & Research Institute | Tampa, Florida 33612 |
| Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco | San Francisco, California 94115 |
