AzTrials
AzTrials

Metastatic Large Cell Neuroendocrine CarcinomaPhase 2NCT04079712

Testing the Combination of XL184 (Cabozantinib), Nivolumab, and Ipilimumab for Poorly Differentiated Neuroendocrine Tumors

A Phase 2 study testing Cabozantinib S-malate, Ipilimumab and Nivolumab in people with Metastatic Large Cell Neuroendocrine Carcinoma and Metastatic Neuroendocrine Carcinoma, run by National Cancer Institute (NCI) at 46 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase II trial studies how well the combination of XL184 (cabozantinib), nivolumab, and ipilimumab work in treating patients with poorly differentiated neuroendocrine tumors (i.e., neuroendocrine tumor that does not look like the normal tissue it arose from). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib S-malate, Ipilimumab and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
46 sitesin 2 countries
Study dates
6 Aug 2020to 2 Sep 2027
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 must have metastatic, histologically confirmed poorly-differentiated neuroendocrine neoplasms per 2018 World Health Organization (WHO) classification, with the exception of small cell lung cancer and Merkel cell carcinoma. All variations of poorly differentiated neuroendocrine carcinoma (small cell, large cell and mixed cells) are eligible
  • Failure of only one line of prior systemic cancer treatment
  • Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
  • Patients must have lesions that can be safely biopsied and be willing to have a pre-treatment and an on-treatment biopsy (after 1 month of treatment with the combination regimen) and a blood collection at baseline
  • Prior systemic cancer therapy must have been completed at least 4 weeks prior to cycle 1 day 1 of treatment with the combination regimen
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Show all 28Show fewer
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL without granulocyte-colony stimulating (GCSF) factor support
  • Hemoglobin >= 9 g/dL
  • Serum thyroid stimulating hormone (TSH) within institutional normal limits
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN); =< 3.0 x ULN for patients with Gilbert's syndrome
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN
  • Alkaline phosphatase =< 3.0 x institutional ULN; =< 5.0 x ULN with documented bone metastases
  • Creatinine =< institutional ULN OR creatinine clearance (CrCl) >= 50 mL/min/1.73 m^2 (using the Cockcroft-Gault formula)
  • Serum albumin >= 2.8 g/dL
  • Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
  • Urine protein/creatinine ratio (UPCR) =< 1 mg protein/mg creatinine
  • Serum phosphorus, calcium, magnesium, and potassium within institutional normal limits
  • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) test < 1.3 x ULN
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy utilizing agents that do not strongly induce or inhibit cytochrome P450 (CYP) 3A4 with undetectable viral load within 6 months prior to study registration are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and are off steroid support for at least 4 weeks after treatment for metastases is complete and within 28 days prior to the first dose of study treatment. Radiotherapy should have been stopped at least 4 weeks prior to study registration. Brain surgery should not have occurred within 3 months of study registration to be eligible
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • The effects of XL184 (cabozantinib), nivolumab, and ipilimumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of study therapy. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity: 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of study therapy. Women must not be breastfeeding. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of < 1% per year. Men who receive study therapy 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 study therapy. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level < 40 mIU/mL. WOCBP and men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 5 and 7 months, respectively, after the last dose of study therapy. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) must inform the treating physician immediately
  • Patients must be able to swallow tablets
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Who cannot join

  • Patients must not require systemic corticosteroids treatment (>= 10 mg/day prednisone equivalents) or other immunosuppressive medications within 28 days prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids in patients with adrenal insufficiency are permitted, even if >= 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as is steroid pre-medication for contrast allergy
  • Patients must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways
  • Patients must not have had prior treatment with XL184 (cabozantinib), or any MET-targeting tyrosine kinase inhibitor (TKI), or any MET-targeting monoclonal antibody (MetMAb), such as onartuzumab
  • Patients must not have received radiation therapy to any part of the body within 28 days
  • Patients must not have clinically relevant, ongoing complications from prior radiation therapy. No radiation therapy is allowed while the patient is on study. Palliative radiation therapy, if needed, should be completed at least 28 days prior to enrollment into the study as described above
  • Patients must not require concomitant treatment with oral anticoagulants (e.g., warfarin, direct thrombin, and factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel). The following anticoagulants are allowed:
Show all 37Show fewer
  • Low-dose aspirin for cardioprotection (per local applicable guidelines),
  • Low-dose low molecular weight heparins (LMWH),
  • Therapeutic doses of LMWH are allowed in patients without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before the first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
  • Patients must not have had major surgery (e.g., gastrointestinal [GI] surgery or removal or biopsy of brain metastasis) within 4 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment and from minor surgery (e.g., simple excision or tooth extraction) at least 10 days before the first dose. Patients with clinically relevant ongoing complications from prior surgery are not eligible
  • Patients must not have received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 4 weeks, or nitrosoureas/ mitomycin C within 4 weeks, before the first dose of study treatment. Patients may continue on bone-modifying agents (denosumab or bisphosphonates) with caution
  • Patients who have not recovered to baseline from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)0.5 unless the adverse events (AEs) are clinically nonsignificant and/or stable on supportive therapy, with the exception of alopecia
  • Patients who are receiving any other investigational agents. Patients must not have received any other type of investigational agent within 4 weeks before the first dose of study treatment to be eligible
  • Patients must not have a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 msec by electrocardiogram (EKG) within 28 days before the first dose of study treatment
  • Note: If a single EKG shows a QTcF with an absolute value > 500 msec, two additional EKGs at intervals of approximately 3 min must be performed within 30 min after the initial EKG, and the average of these three consecutive results for QTcF will be used to determine eligibility
  • Patients should not have known, untreated brain metastases or leptomeningeal metastases because of poor prognosis and concerns that progressive neurologic dysfunction could confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
  • Patients must not have a history of severe hypersensitivity reactions to any monoclonal antibodies
  • Patients must not require concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, or St. John's wort). Because lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, patients will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients must not have uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Congestive heart failure New York Heart Association (NYHA) Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment within seven days prior to the first dose of study treatment.
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis [DVT], pulmonary embolism [PE]) within 6 months before first dose.
  • GI disorders including those associated with a high risk of perforation or fistula formation:
  • The patient has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
  • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Complete healing of an intra-abdominal abscess must be confirmed before first dose.
  • Clinically significant hematuria, hematemesis, or hemoptysis or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Lesions invading or encasing any major blood vessels.
  • Other clinically significant disorders that would preclude safe study participation.
  • Serious non-healing wound/ulcer/bone fracture.
  • Uncompensated/symptomatic hypothyroidism.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because XL184 (cabozantinib) has the potential for teratogenic or abortifacient effects, and the effects of nivolumab and ipilimumab on the developing fetus are not well known. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued if the mother is treated with XL184 (cabozantinib), nivolumab, or ipilimumab
  • Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including high dose systemic corticosteroids, should be excluded. These include but are not limited to: immune-related neurologic disease, such as multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, or myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, or autoimmune hepatitis. Patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, type I diabetes mellitus (DM), or endocrine deficiencies (e.g., thyroiditis) managed with replacement hormones, including physiologic corticosteroids, are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication, and patients with positive serology, (e.g., antinuclear antibodies [ANA] or anti-thyroid antibodies) should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

Trial locations and contacts

46 sites in 2 countries.

46 sites in 2 countries

United States45 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Northwestern University

    Chicago, Illinois, 60611

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Wake Forest University at Clemmons

    Clemmons, North Carolina, 27012

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Farmington Health Center

    Farmington, Utah, 84025

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • HaysMed

    Hays, Kansas, 67601

  • University Health Truman Medical Center

    Kansas City, Missouri, 64108

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • The University of Kansas Cancer Center - Olathe

    Olathe, Kansas, 66061

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • Mercy Hospital Pittsburg

    Pittsburg, Kansas, 66762

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • University of Utah Sugarhouse Health Center

    Salt Lake City, Utah, 84106

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Kansas Health System Saint Francis Campus

    Topeka, Kansas, 66606

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, 85719

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Wake Forest Baptist Health - Wilkes Medical Center

    Wilkesboro, North Carolina, 28659

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 2 Study of XL184 (Cabozantinib) in Combination With Nivolumab and Ipilimumab for the Treatment of Poorly Differentiated Neuroendocrine Carcinomas

This phase II trial studies how well the combination of XL184 (cabozantinib), nivolumab, and ipilimumab work in treating patients with poorly differentiated neuroendocrine tumors (i.e., neuroendocrine tumor that does not look like the normal tissue it arose from). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab and ipilimumab may shrink the cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the overall response rate (ORR) associated with the combination of XL184 (cabozantinib), nivolumab, and ipilimumab in patients with advanced poorly-differentiated neuroendocrine carcinomas (NECs), after the failure of at least one line of prior therapy.

SECONDARY OBJECTIVES:

  1. To evaluate progression-free survival (PFS). II. To measure the safety and tolerability of the combination of XL184 (cabozantinib), nivolumab, and ipilimumab in patients with advanced, poorly-differentiated NECs.

III. To evaluate disease control rate (DCR). IV. To measure duration of response (DOR). V. To describe the tumor molecular profile using whole exome sequencing (WES) and correlate it with treatment outcome.

VI. To describe the tumor molecular profile using ribonucleic acid (RNA) sequencing (RNAseq) and correlate it with treatment outcome.

EXPLORATORY OBJECTIVES:

  1. To measure the tumor-infiltrating CD8+ T lymphocytes in pre- and on-treatment biopsies.

II. To measure tumor-infiltrating myeloid derived suppressor cells (MDSCs) in pre- and on-treatment biopsies.

III. To measure tumor-infiltrating tumor-associated macrophages (TAM) in the pre and on-treatment biopsies.

IV. To measure the expression of programmed death-ligand 1 (PD-L1) in tumor cells and infiltrating immune cells.

OUTLINE:

Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-21 of cycles 1-4 and days 1-28 of subsequent cycles, nivolumab intravenously (IV) over 30 minutes on day 1, and ipilimumab IV over 90 minutes on day 1 of cycles 1-4 only. Treatment repeats every 21 for 4 cycles then every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, and then every 3 months thereafter.

Being tested
Cabozantinib S-malate, Ipilimumab, Nivolumab
Medical subject headings
Carcinoma, Neuroendocrine, Neuroendocrine Tumors, Small Cell Lung Carcinoma

What participants receive

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

  • Cabozantinib S-malateDrug

    Also called BMS-907351, Cabometyx, Cometriq, XL 184

    Given PO

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016

    Given IV

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

Study groups in NCT04079712
Study groupRoleWhat they receive
Treatment (cabozantinib s-malate, nivolumab, ipilimumab)ExperimentalPatients receive cabozantinib s-malate PO QD on days 1-21 of cycles 1-4 and days 1-28 of subsequent cycles, nivolumab IV over 30 minutes on day 1, and ipilimumab IV over 90 minutes on day 1 of cycles 1-4 only. Treatment repeats every 21 for 4 cycles then every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cabozantinib S-malate; Biological: Ipilimumab; Biological: Nivolumab

What is being measured

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

  1. Number of Participants With a Response

    Participants who are considered to have a response are those with either a complete response (CR) (disappearance of all target lesions) or a partial response (PR) (>=30% decrease in the sum of the longest diameter of target lesions) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and assessed by CT or MRI scan.

    Measured: Up to 3.5 years

Secondary outcomes (4)

  1. Progression Free Survival (PFS)

    Progression is defined as a >= 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) and assessed by CT or MRI scan. The duration is from the date of registration to the time of progression or death, whichever occurs first.

    Measured: Up to 3.5 years

  2. Number of Participants Reporting Adverse Events

    Adverse events will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria. The population is defined as all patients who have received the study treatment. The highest grade is reported.

    Measured: Up to 3.5 years

  3. Disease Control Rate (DCR)

    DCR will be defined as the achievement of Complete Response (CR) (disappearance of all target lesions), Partial Response (PR) (>=30% decrease in the sum of the longest diameter of target lesions), or Stable Disease (SD) (between < 30% decrease and >20% increase in the sum of the longest diameter of target lesions) using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI scan.

    Measured: Up to 3.5 years

  4. Duration of Response (DOR)

    The time when measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.

    Measured: Up to 3.5 years

Timeline

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

  1. First posted6 Sep 2019
  2. Study start6 Aug 2020
  3. Primary completion10 Jan 2025
  4. Study completion2 Sep 2027 (estimated)

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
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04079712
Sponsor's protocol ID
NCI-2019-05864
Other IDs
NCI-2019-05864, 10315, 10315, UM1CA186689, UM1CA186691
Status last verified
Sep 2026
First submitted
4 Sep 2019
Last updated
22 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Publications

  • Mandl A, Chen R, Das S, Strosberg JR, Kasi A, Konda B, Li D, Burns TF, Chauhan A, Ciombor KK, Dayyani F, Dorff T, Ohr JP, Patel BB, Sukrithan V, Soares HP, Chen K, Liu SV, Tesfaye AA, Carducci MA, Beumer JH. Phase 2 study of cabozantinib (XL184) with nivolumab and ipilimumab for the treatment of poorly differentiated neuroendocrine carcinomas (ETCTN10315). Oncologist. 2026 May 8;31(6):oyag140. doi: 10.1093/oncolo/oyag140.

    PubMed 41968073

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib S-malate, Ipilimumab and Nivolumab in people with Metastatic Large Cell Neuroendocrine Carcinoma and Metastatic Neuroendocrine Carcinoma, run by National Cancer Institute (NCI) at 46 sites in 2 countries.

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 28 inclusion and 37 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: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in United States, Canada. 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 12 Dec 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?

Number of Participants With a Response (time frame: Up to 3.5 years). 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 NCT04079712, which also lists 1 linked publication.

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 22 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in