Cabozantinib and Nivolumab for Carcinoid Tumors

NCT04197310 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-403
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

This research study, is studying the combination of cabozantinib and nivolumab in treating advanced carcinoid tumors. \- Carcinoid tumor is another term used to refer to neuroendocrine tumors that arise in organs such as the gastrointestinal tract, lungs, or thymus.

Conditions

Carcinoid Tumor; Carcinoid Tumor of GI System; Neuroendocrine Tumors

Keywords

Carcinoid Tumor; Carcinoid Tumor of GI System; Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined by RECIST 1.1 criteria, the percentage of subjects with a confirmed complete response or partial response at any time during treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the diameters of target lesions; Overall Response (OR) = CR + PR.

  46 months

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  Time from randomization (or registration) to the earlier of progression or death due to any cause. The median survival follow-up time was 5.6 months (range 1.4 - 31.0 months).

• Overall Response Rate (ORR) Per Immune-related Response Criteria

  46 months

• Overall Survival (OS)

  Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. OS was calculated for a median of 6.9 months, ranging from 2.8 - 31.0 months.

• Number of Participants With Treatment Related Adverse Events

  AEs were reviewed between the initial dose of study treatment and 100 days of the last dose of treatment. AEs were assessed for a median of 8.8 months, ranging from 4.7 - 33.7 months.

• Duration of Response

  The median survival follow-up time was 5.6 months (range 1.4 - 31.0 months).

Study Arms (1)

Nivolumab and Cabozantinib

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Cabozantinib will be administered at a dose of 40mg orally, once daily * Nivolumab will be given at a dose of 240mg every 14 days, intravenously Retreat Phase (Optional) * Participants may elect to stop nivolumab and cabozantinib with confirmed CR after at least 24 weeks of treatment. * Participants who elect to stop and then the condition progresses after stopping study treatment may be eligible to resume nivolumab and cabozantinib therapy. * This resumption will be termed as a retreatment second course phase and is available only while the study remains open and the subject meets specified criteria.

Drug: Nivolumab; Drug: Cabozantinib

Interventions

Nivolumab DRUG

240mg, intravenously, Day 1 and 15 of a 28 day cycle

Also known as: Opdivo

Nivolumab and Cabozantinib

Cabozantinib DRUG

40mg, orally, Daily for a 28 day cycle

Also known as: Cometriq, Cabometyx

Nivolumab and Cabozantinib

Eligibility Criteria

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

You may qualify if:

• Patients with locally unresectable or metastatic well-differentiated neuroendocrine tumor of non-pancreatic (ie, carcinoid) origin
• Participants 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 for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
• Patients must have evidence of radiographic disease progression within the past 12 months.
• Patients who have received at least one line of therapy, which can include somatostatin analog therapy. Participants should be adequately recovered from acute toxicities of prior treatment.
• Prior somatostatin analog therapy is allowed. Continuation of somatostatin analog therapy is allowed provided that the dose has been stable for 2 months.
• Prior chemotherapy: Participants must have been off treatment with cytotoxic chemotherapy for at least 14 days prior to registration.
• Prior biologic therapy: Patients must have discontinued all biologic therapy at least 28 days prior to registration. Duration may be shorted to 14 days for agents with short half-lives.
• Prior radiolabeled somatostatin analog therapy: Participants must have completed radiolabeled somatostatin analog therapy at least 6 weeks prior to registration.
• Prior hepatic artery embolization or ablative therapies is allowed if measurable disease remains outside the treated area or there is documented disease progression in a treated site. Prior liver-directed or ablative treatment must be completed at least 28 days prior to registration.
• Prior radiation therapy: Radiation therapy must be completed per the following timelines
• i) Radiotherapy to the thoracic cavity or abdomen within 4 weeks prior to registration.
• ii) Radiotherapy to bone lesions within 2 weeks prior to registration.
• iii) Radiotherapy to any other site within 4 weeks prior to registration.
• NOTE: In all cases, there must be complete recovery and no ongoing complications from prior radiotherapy.
• Age ≥ 18 years.

You may not qualify if:

• Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
• Participants who are receiving any other investigational agents.
• Participants who have received a prior cabozantinib.
• Participants who have received prior therapy with an anti-PD-1, anti-PD-L1, anti- PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including nivolumab, pembrolizumab, ipilimumab, and any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• The participant has tumor in contact with, invading, or encasing major blood vessels or radiographic evidence of significant cavitary pulmonary lesions.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib or nivolumab.
• Participants receiving any strong inhibitors or inducers of CYP3A4 within 14 days prior to registration are ineligible. Chronic treatment with strong inhibitors or inducers of CYP3A4 is not allowed.
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening;
• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;
• Any history of congenital long QT syndrome;
• QTcF interval \>500 msec
• Any of the following within 6 months before the first dose of study treatment:
• unstable angina pectoris;

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator
• Exelixis: collaborator

Study Sites (2)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Carcinoid Tumor; Neuroendocrine Tumors

Interventions

Nivolumab; cabozantinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Kimberly Perez
• Organization: Dana Farber Cancer Institute

Kimberly_Perez@DFCI.HARVARD.EDU

617-632-5960

Study Officials

• Kimberly Perez, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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 11, 2019
• First Posted: December 13, 2019
• Study Start: December 26, 2019
• Primary Completion: December 27, 2023
• Study Completion: January 31, 2024
• Last Updated: January 31, 2025
• Results First Posted: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)