Cabozantinib in Recurrent/Metastatic Merkel Cell Carcinoma

Study Description

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Brief Summary:

This is an open-label, non-randomized, phase 2 study to assess the feasibility of using cabozantinib in recurrent/metastatic Merkel Cell Carcinoma patients that progressed after platinum-based therapy.

Condition or disease	Intervention/treatment	Phase
Merkel Cell Carcinoma; Skin Cancer	Drug: Cabozantinib	Phase 2

Detailed Description:

Cabozantinib (XL184) is an inhibitor of multiple receptor tyrosine kinases and was approved by the U.S. Food and Drug Administration (FDA) on 29 November 2012 for the treatment of patients with progressive, metastatic medullary thyroid cancer. It is commercially available as COMETRIQ™ in the United States.

During the Pre Treatment Period, participants are consented and qualified (screened) for the study. Treatment will be administered on an outpatient basis.

Each treatment cycle lasts 28 days, during which time the participant will be taking the study drug, cabozantinib, once daily. The participant will be given a study drug-dosing diary for each treatment cycle. The diary will also include special instructions for taking the study drug.

- Participants will be followed for 8 weeks after removal from study or until death, whichever occurs first. Participants removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	8 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Cabozantinib in Recurrent/Metastatic Merkel Cell Carcinoma
Actual Study Start Date :	January 2014
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	January 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Cabozantinib; Cabozantinib 60 mg Oral Daily 28 days (4 weeks)	Drug: Cabozantinib; Cabozantinib 60 mg Oral Daily 28 days (4 weeks); Other Names: XL184; Cometriq

Outcome Measures

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Primary Outcome Measures :

1. Disease Control Rate [ Time Frame: 3 Months ]
   The disease control rate is defined as the rate of complete response (CR), partial response (PR), or stable disease (SD) as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Secondary Outcome Measures :

1. Progression-Free and Overall Survival [ Time Frame: 2 Years ]
   To determine progression-free survival and overall survival of patients receiving cabozantinib for Merkel Cell Carcinoma.
2. Adverse Events [ Time Frame: 2 Years ]
   To determine the frequency and severity of adverse events as assessed by using common terminology criteria for adverse events (CTCAE) version 4.0.
3. Expression of c-MET, phospho-MET and VEGFR-2 on tumor tissue [ Time Frame: 2 Years ]
   To retrospectively correlate the expression of c-MET, phospho-MET and VEGFR-2 on tumor tissue with clinical outcome.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Must have histologically or cytologically confirmed Merkel Cell Carcinoma that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
• Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan (see section 10 for the evaluation of measureable disease). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented
• Must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin or another organoplatinum compound. Patients are also eligible if they received curative intent platinum-based therapy and progressed within a year of therapy
• No prior MET inhibitor is allowed
• At least 2 weeks since prior chemotherapy or radiation therapy. At least 3 weeks since prior biologics or investigational agents
• Recovery from effects of recent treatment to baseline or CTCAE ≤ grade 1 toxicity from all prior therapies except alopecia and other non-clinically significant AEs
• Participants must be ≥18 years of age
• ECOG performance status ≤1
• Participants must have normal organ and marrow function
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
• Ability to understand and the willingness to sign a written informed consent document
• Collection of archival tissue specimens for confirmation of Merkel Cell Carcinoma

Exclusion Criteria:

• Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
• Participants may not be receiving any biologics or investigational agents within 3 weeks
• The subject has active brain metastases or epidural disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib
• Has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥ 1.3 the institutional ULN within 7 days before the first dose of study treatment, unless PT/PTT prolongation known to be secondary to conditions not associated with increased bleeding risk (as on antiphospholipid antibody syndrome)
• Requires concomitant treatment, in therapeutic doses, with anticoagulants
• Active bleeding or pathologic conditions that carry high risk of bleeding
• Have experienced clinically significant gastrointestinal bleeding within 6 months before first dose of study treatment
• Requires chronic concomitant treatment of strong CYP3A4 inducers
• Is unable or unwilling to swallow tablets
• Has a corrected QT interval calculated by the Fridericia formula (QTcF)>500 ms within 28 days before initiation of cabozantinib
• Has evidence of tumor invading the GI tract or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
• Has radiographic evidence of cavitating pulmonary lesion(s)
• Has uncontrolled, significant intercurrent or recent illness
• Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy
• History of major surgery within 3 months or minor surgery within 1 month of the first dose of cabozantinib
• Pregnant women
• Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy
• HIV-positive individuals on combination antiretroviral therapy

Contacts and Locations

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Locations

United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Dana-Farber Cancer Institute

Exelixis

Investigators

Principal Investigator:	Guilherme Rabinowits, MD	Brigham and Women's Hospital

More Information

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Responsible Party:	Guilherme Rabinowits, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT02036476 History of Changes
Other Study ID Numbers:	13-490
First Posted:	January 15, 2014
Last Update Posted:	February 16, 2018
Last Verified:	February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No
Plan Description:	There are no plans to share individual participant data. Cumulative results will be posted here and published.

Keywords provided by Guilherme Rabinowits, Dana-Farber Cancer Institute:

Merkel Cell Carcinoma; Skin Cancer

Additional relevant MeSH terms:

Carcinoma; Skin Neoplasms; Carcinoma, Merkel Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Skin Diseases; Polyomavirus Infections	DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Nerve Tissue