Cabozantinib and Nivolumab for Carcinoid Tumors

  • STATUS
    Recruiting
  • End date
    Dec 26, 2023
  • participants needed
    35
  • sponsor
    Dana-Farber Cancer Institute
Updated on 24 March 2022
ct scan
measurable disease
somatostatin
gilbert's syndrome
metastasis
neutrophil count
cabozantinib
nivolumab
spiral computed tomography
line of therapy
metastatic cancer
neuroendocrine tumor
hepatic artery embolization
carcinoid tumor

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.

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.

Details
Condition Carcinoid Tumor, Carcinoid Tumor of GI System, Neuroendocrine Tumors
Treatment Nivolumab, Cabozantinib
Clinical Study IdentifierNCT04197310
SponsorDana-Farber Cancer Institute
Last Modified on24 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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, antiPD -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
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
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