NCT01835145|CompletedPhase 2Results

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

National Cancer Institute (NCI)ClinicalTrials.gov

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5 other identifiers

NCI-2013-00821CALGB-A091201A091201U10CA180821U10CA031946

Study Type

interventional

Target

Locations

2 countries

Sites

228

Timeline

RegisteredApr 2013

StartedJul 2013

CompletionNov 2019

Brief Summary

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

Completed

Started Jul 2013

Longer than P75 for phase_2

Geographic Reach

2 countries

228 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.3 years study duration

First Submitted

Initial submission to the registry

April 16, 2013

Completed

2 days until next milestone

First Posted

Study publicly available on registry

April 18, 2013

Completed

3 months until next milestone

Study Start

First participant enrolled

July 31, 2013

Completed

3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 21, 2016

Completed

2.5 years until next milestone

Results Posted

Study results publicly available

April 26, 2019

Completed

6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2019

Completed

Last Updated

August 4, 2022

Status Verified

August 1, 2022

Enrollment Period

3.2 years

First QC Date

April 16, 2013

Results QC Date

July 31, 2018

Last Update Submit

August 3, 2022

Conditions

Recurrent Uveal Melanoma Stage III Uveal Melanoma AJCC v7 Stage IIIA Uveal Melanoma AJCC v7 Stage IIIB Uveal Melanoma AJCC v7 Stage IIIC Uveal Melanoma AJCC v7 Stage IV Uveal Melanoma AJCC v7

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (4)

Confirmed Response Rate as Determined by the RECIST Criteria (Version 1.1)
Up to 2 years
Percentage of Patients Who Experienced Grade 3+ Adverse Events Regardless of Attribution
Up to 2 years
Overall Survival (OS)
Number of days from registration until death, assessed up to 2 years
PFS
Number of days from registration until disease progression (or death), assessed up to 2 years

Other Outcomes (2)

Pre-treatment GNAQ/GNA11 and Potentially Other Mutations in Tissue
Baseline
Pre-treatment Immune Gene Expression in Tissue Defined as T Cell-inflamed, Intermediate and Non-T Cell-inflamed
Baseline

Study Arms (2)

Arm I (cabozantinib-s-malate)

EXPERIMENTAL

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.

Drug: Cabozantinib S-malateOther: Laboratory Biomarker Analysis

Arm II (temozolomide or dacarbazine)

EXPERIMENTAL

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.

Drug: DacarbazineOther: Laboratory Biomarker AnalysisDrug: Temozolomide

Interventions

Cabozantinib S-malateDRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL-184, XL184

Arm I (cabozantinib-s-malate)

DacarbazineDRUG

Given IV

Also known as: 4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine, Dacarbazina, Dacarbazina Almirall, Dacarbazine - DTIC, Dacatic, Dakarbazin, Deticene, Detimedac, DIC, Dimethyl (triazeno) imidazolecarboxamide, Dimethyl Triazeno Imidazol Carboxamide, Dimethyl Triazeno Imidazole Carboxamide, dimethyl-triazeno-imidazole carboxamide, Dimethyl-triazeno-imidazole-carboximide, DTIC, DTIC-Dome, Fauldetic, Imidazole Carboxamide, Imidazole Carboxamide Dimethyltriazeno, WR-139007

Arm II (temozolomide or dacarbazine)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (cabozantinib-s-malate)Arm II (temozolomide or dacarbazine)

TemozolomideDRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Arm II (temozolomide or dacarbazine)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Histologically or cytologically confirmed uveal melanoma that is metastatic or unresectable; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of diagnosis will be performed at the participating site
Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI)
Prior systemic therapies allowed, except for those treatments directed toward, or with activity against, c-Met or vascular endothelial growth factor/receptor (VEGF/R), and the chemotherapy agents temozolomide and dacarbazine; prior treatment must have been no earlier than 3 weeks prior to starting treatment with cabozantinib with exceptions noted below and the following: at least 4 weeks since prior hepatic infusion or at least 2 weeks since radiation therapy
No cytotoxic chemotherapy including investigational cytotoxic chemotherapy or biologic agents (e.g., cytokines or antibodies) within the last 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment; at least 6 weeks must have elapsed if the last regimen included an anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody; patients must have experienced disease progression on their prior therapy in the opinion of the treating investigator
No prior radiation therapy within the last 4 weeks, except as below
To the thoracic cavity, abdomen, or pelvis within 12 weeks before the first dose of study treatment, or has ongoing complications, or is without complete recovery to \< grade 1 toxicity
To bone or brain metastasis within 14 days before the first dose of study treatment
To any other site(s) within 28 days before the first dose of study treatment
Prior radiation treatment may have included no more than 3000 centigray (cGy) to fields including substantial bone marrow
No prior radionuclide treatment within 6 weeks of the first dose of study treatment
No prior treatment with a small molecule kinase inhibitor or a hormonal therapy within 14 days or 5 half-lives (whichever is longer)
No concomitant anti-cancer therapy unless specified above
Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
A corrected QT interval calculated by the Fridericia formula (QTcF) =\< 500 ms within 28 days before randomization; Note: if initial QTcF is found to be \> 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is =\< 500 ms, the patient meets eligibility in this regard
Common Terminology Criteria for Adverse Events (CTCAE) recovered to baseline or CTCAE =\< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
+72 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead
Exelisiscollaborator

Study Sites (228)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC