Cabozantinib in Recurrent/Metastatic Merkel Cell Carcinoma

NCT02036476 | Terminated Phase 2 Results DMC

• 1 other identifier: 13-490
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

Conditions

Merkel Cell Carcinoma; Skin Cancer

Keywords

Merkel Cell Carcinoma; Skin Cancer

Outcome Measures

Primary Outcomes (1)

• 3-Month Disease Control Rate (DCR)

  3-month DCR is the percentage of participants achieving complete response (CR), partial response (PR) or stable disease (SD) during first 3 months of treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria and lasting at least 3 months from baseline.

  Disease was assessed on day 1 of weeks 3, 5, 7, 9, 11, 13 then every 4 weeks on treatment. Relative to this endpoint was observation up to 3 months on treatment. Length of longest follow up was 83 days.

Secondary Outcomes (3)

• 3-month Progression-free Survival (PFS)

  Assessed every 2 weeks (w) from cycles 3-13 and then every 4w, day 30-37 post-treatment end and up to 8w in long-term follow-up. Length of longest follow up for the KM estimate was 126 days. Relative to this endpoint was 3-month probability.

• 3-Month Overall Survival (OS) Rate

  3 months

• Grade 3-5 Treatment-Related Adverse Event (AE) Rate

  Up to 126 days

Study Arms (1)

Cabozantinib

EXPERIMENTAL

Cabozantinib 60 mg given orally daily for 28 days (4 weeks) each cycle. Participants were treated until disease progression, unacceptable toxicity or withdrawal for other reasons.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

oral administration

Also known as: XL184, Cometriq

Cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Exelixis: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Rabinowits G, Lezcano C, Catalano PJ, McHugh P, Becker H, Reilly MM, Huang J, Tyagi A, Thakuria M, Bresler SC, Sholl LM, Shapiro GI, Haddad R, DeCaprio JA. Cabozantinib in Patients with Advanced Merkel Cell Carcinoma. Oncologist. 2018 Jul;23(7):814-821. doi: 10.1634/theoncologist.2017-0552. Epub 2018 Feb 14.

  PMID: 29445030 RESULT

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Skin Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study is limited by the small sample size and single-arm design along with early termination given slow accrual, lack of response and poor tolerability.

Results Point of Contact

• Title: Dr. Robert Haddad
• Organization: Dana-Farber Cancer Institute

ROBERT_HADDAD@DFCI.HARVARD.EDU

617.632.3090

Study Officials

• Robert Haddad, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 19, 2013
• First Posted: January 15, 2014
• Study Start: February 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 9, 2023
• Results First Posted: May 9, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)