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Carcinoid TumorPhase 2NCT04197310

Cabozantinib and Nivolumab for Carcinoid Tumors

A Phase 2 study testing Nivolumab and Cabozantinib in people with Carcinoid Tumor and Carcinoid Tumor of GI System, run by Dana-Farber Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab and Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
2 sitesUnited States
Study dates
26 Dec 2019to 31 Jan 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • ECOG performance status ≤1 (Karnofsky ≥60%, see Appendix A)
  • Participants must have normal organ and marrow function as defined below:
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • total bilirubin ≤1.5 × institutional upper limit of normal (ULN) (or 2.0 x ULN in patients with documented Gilbert's Syndrome)
  • AST (SGOT)/ALT (SGPT) ≤2.5 × ULN or ≤ 3 × ULN for participants with documented liver metastases
  • creatinine <1.5 × ULN Or creatinine clearance ≥40 mL/min (using Cockcroft-Gault formula) for participants with creatinine levels above institutional normal
  • Urine protein/creatinine ratio (UPCR) ≤ 1
  • PT/INR or partial thromboplastin time (PTT) test < 1.3 the laboratory ULN within 7 days before the first dose of study treatment.
  • Negative urine pregnancy test for women of childbearing potential.
  • Participant must be able to swallow pills.
  • The participant is capable of understanding and complying with the protocol and has signed the informed consent document.

Who cannot join

  • 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.
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  • 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;
  • clinically-significant cardiac arrhythmias;
  • stroke (including transient ischemic attack (TIA), or other ischemic event);
  • myocardial infarction;
  • GI disorders particularly those associated with a high risk of perforation or fistula formation including:
  • Tumors invading the GI tract, active peptic ulcer disease, active inflammatory bowel disease (eg, Crohn's disease), active diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
  • Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before screening
  • Thromboembolic events within 6 months of registration.
  • Note: Low dose aspirin ≤ 81 mg/day is allowed. Anticoagulation with therapeutic doses of LMWH is allowed in patients who are on a stable dose of LMWH for at least 6 weeks prior to registration. Treatment with warfarin is not allowed.
  • The subject has experienced any significant bleeding episodes, including:
  • Clinically significant gastrointestinal bleeding within 6 months before the first dose of study treatment
  • Clinically significant hemoptysis (> 0.5 teaspoon) within 3 months of the first dose of study treatment
  • Any other signs indicative of pulmonary hemorrhage within 3 months before the start of study treatment
  • Individuals with a history of different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the investigator to be at low risk for recurrence of that malignancy.
  • Participant has an active infection requiring IV antibiotics
  • Any active, known, or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (e.g. celiac disease) are permitted to enroll.
  • Patient has a medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. Adrenal replacement steroid disease are permitted in the absence of autoimmune disease.
  • The participant is known to be positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants with non-detectable viral loads on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cabozantinib and nivolumab.
  • The participant has received a live vaccine within 28 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. The use of the inactivated seasonal influenza vaccine (Fluzone®) is allowed.
  • Pregnant or lactating females are excluded from this study because cabozantinib and nivolumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib and nivolumab, breastfeeding should be discontinued if the mother is treated with cabozantinib and nivolumab. These potential risks may also apply to other agents used in this study.
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and following treatment. Women of childbearing potential receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab. Contraception must be used for 4 months after last dose of cabozantinib.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Phase II Trial of Cabozantinib in Combination With Nivolumab for Advanced Carcinoid Tumors

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.
Read the detailed description

This is open-label, single-arm, phase II research study, 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.

  • The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
  • Cabozantinib will be administered orally, once daily
  • Nivolumab will be administered intravenously, every two weeks
  • The target enrollment for this study is 35 participants.
  • The U.S. Food and Drug Administration (FDA) has not approved cabozantinib or nivolumab for treating carcinoid tumors.
Being tested
Nivolumab, Cabozantinib
Keywords
Carcinoid Tumor, Carcinoid Tumor of GI System, Neuroendocrine Tumors
Medical subject headings
Carcinoid Tumor, Neuroendocrine Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo

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

  • CabozantinibDrug

    Also called Cometriq, Cabometyx

    40mg, orally, Daily for a 28 day cycle

Study groups in NCT04197310
Study groupRoleWhat they receive
Nivolumab and CabozantinibExperimentalThe 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.
Receives: Drug: Nivolumab; Drug: Cabozantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 46 months

Secondary outcomes (5)

  1. Progression-free Survival (PFS)

    Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesion and/or unequivocal progression of existing non-target lesions are also considered progression. Unequivocal progression should not normally trump target lesion status and must be representative of overall disease status change, not a single lesion increase.

    Measured: 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).

  2. Overall Response Rate (ORR) Per Immune-related Response Criteria

    ORR will be determined according to immune-related response criteria (irRC). irComplete Response (irCR): Complete disappearance of all target lesions. irPartial Response (irPR): Decrease, relative to baseline, or 50% or greater in the sum of the products of the two largest perpendicular diameters of all target and all new measurable target lesions. irStable Disease (irSD): Does not meet criteria for irRC or irPR, in the absence of progressive disease. irProgressive Disease (irPD): At least 25% increase Percentage Change in Tumor Burden when compared to SPD at nadir.

    Measured: 46 months

  3. Overall Survival (OS)

    Kaplan and Meier to assess Overall survival (OS).

    Measured: 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.

  4. Number of Participants With Treatment Related Adverse Events

    Safety was assessed by analysis of adverse event (AE) and toxicity data. AE and toxicity data are defined according to NCI CTCAE version 5.0. Adverse Events were reviewed between the initial dose of study treatment and 100 days of the last dose of treatment. All adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms will be counted. Rate is the proportion of treated participants experiencing at least one treatment-related AE of any type during the time of observation.

    Measured: 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.

  5. Duration of Response

    To evaluate duration of response of participants receiving Nivolumab and Cabozatinib. Duration of response was evaluated from date of registration to date of death or last known date alive.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2019
  2. Study start26 Dec 2019
  3. Primary completion27 Dec 2023
  4. Study completion31 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04197310
Sponsor's protocol ID
19-403
Status last verified
Jan 2025
First submitted
11 Dec 2019
Last updated
31 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Cabozantinib in people with Carcinoid Tumor and Carcinoid Tumor of GI System, run by Dana-Farber Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: 46 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04197310.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.

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