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All Drugs and Chemicals

Antineoplastic Agents

Imidazole

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Dacarbazine

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Alkylating Agents

Enzyme Inhibitors

Patients receive cabozantinib-s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive temozolomide PO daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. If temozolomide is not available, patients receive dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cabozantinib S-malate

Laboratory Biomarker Analysis

Jason J Luke

This randomized phase II trial studies how well cabozantinib-s-malate works compared with temozolomide or dacarbazine in treating patients with melanoma of the eye (ocular melanoma) that has spread to other parts of the body and cannot be removed by surgery. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether cabozantinib-s-malate works better than temozolomide or dacarbazine in treating patients with melanoma of the eye.

PRIMARY OBJECTIVES:

I. Compare the progression-free survival rate at 4 months (PFS4) of patients with ocular melanoma treated with cabozantinib-s-malate (cabozantinib) or temozolomide (or dacarbazine).

SECONDARY OBJECTIVES:

I. Estimate the distribution of progression-free survival (PFS) times. II. Estimate the distribution of overall survival (OS) times. III. Estimate the confirmed response rate as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

IV. Assess the safety of these agents by examining the toxicity profile. V. Correlate the response of MET molecular status.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cabozantinib-s-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive temozolomide PO daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. If temozolomide is not available, patients receive dacarbazine intravenously (IV) over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 2 years.

Cabozantinib-S-Malate Compared With Temozolomide or Dacarbazine in Treating Patients With Metastatic Melanoma of the Eye That Cannot Be Removed by Surgery

Randomized Phase II Study Comparing the MET Inhibitor Cabozantinib to Temozolomide/Dacarbazine in Ocular Melanoma

The proportions of patients within these groups pre-treatment will be presented with 90% exact binomial confidence intervals. These findings will be correlated with overall survival using a Student's T-test.

A patient will be declared a PFS4 success if they are on study and progression free for at least 4 months. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. The success for each arm will be calculated independently as the number of successes divided by the total number of evaluable patients. A one-sided chi-squared test for a difference in PFS4 proportions will be used to test for a difference between arms.

The confirmed response rates will be estimated by dividing the number of confirmed responders by the number of evaluable patients. 95% confidence intervals will be calculated.

percentage of patients who experienced grade 3+ adverse events regardless of attribution, graded according to the National Cancer Institute CTCAE version 4.0

The distribution of OS time will be estimated using the method of Kaplan Meier.

The distribution of PFS time will be estimated using the method of Kaplan Meier and is defined as the number of days from registration until disease progression (or death). Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, with an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Exelisis

National Cancer Institute (NCI)

Patients receive 60 mg cabozantinib-s-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arm I (Cabozantinib-s-malate)

Patients receive 150 mg/m\^2 temozolomide PO daily on days 1-5 of a 28 day cycle. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arm II (Temozolomide)

Patients receive 1000 mg/m\^2/day dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm II (Dacarbazine)

Patients receive 150 mg/m\^2 temozolomide PO daily on days 1-5 of a 28 day cycle. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. \>\>

\>\> If temozolomide is not available, patients receive 1000 mg/m\^2/day dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm II (Temozolomide or Dacarbazine)

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Canada

United States

Region of Enrollment

All participants that began study treatment are included in the baseline analysis.

Jason J. Luke, M.D.

A one-sided chi-squared test for a difference in PFS4 rates will be used to test for a difference between arms.

Patients receive 150 mg/m\^2 temozolomide PO daily on days 1-5 of a 28 day cycle. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

\>

\> If temozolomide is not available, patients receive 1000 mg/m\^2/day dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

All patients that began protocol treatment were included in this analysis.

Proportion of Patients Without a Progression Free Survival Event at 4 Months (PFS4)

Patients receive 150 mg/m\^2 temozolomide PO daily on days 1-5 of a 28 day cycle. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

If temozolomide is not available, patients receive 1000 mg/m\^2/day dacarbazine IV over 15-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Spots Global Cancer Trial Database for stage iiia uveal melanoma ajcc v7