Melanoma Clinical Trial

Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery

Summary

This phase II trial tests whether nivolumab in combination with cabozantinib works in patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving nivolumab in combination with cabozantinib could prevent cancer from returning.

View Full Description

Full Description

PRIMARY OBJECTIVE:

I. To compare the efficacy of adjuvant nivolumab (480 mg every [q]4 weeks) versus nivolumab plus cabozantinib s-malate (cabozantinib) (40 mg daily) in patients with mucosal melanoma.

SECONDARY OBJECTIVES:

I. To compare overall survival between the two adjuvant therapies. II. To evaluate the adverse effects in each arm. III. To assess the correlation between PD-L1 expression in tumor cells with survival (recurrence free survival [RFS] and overall survival [OS]).

IV. To evaluate the overall response rate (ORR), duration of response (DOR), progression free survival (PFS), and OS of nivolumab plus cabozantinib in patients who cannot undergo gross total resection of disease or have metastatic disease at baseline.

V. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue.

OUTLINE: Patients whose tumor has been fully removed by surgery are randomized to Arm 1 or Arm 2. Patients whose tumor has not been fully removed by surgery or has spread are assigned to Arm 3.

ARM 1: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and cabozantinib orally (PO) once daily (QD) of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

ARM 3: Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycle in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until disease progression, and then every 6 months for up to 5 years from registration or until death.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

STEP 0 INCLUSION CRITERIA
Histologically proven mucosal melanoma by local pathology
Central PD-L1 tumor tissue submission
STEP 1 INCLUSION CRITERIA
Receipt of the central PD-L1 testing results available

Disease status-Resected R0 or R1 disease patients. Patients eligible for randomization have resected R0 or R1 disease (with negative margins or positive microscopic margins) that must meet one of the following 4 criteria as defined below:

Regional lymph node (LN) involvement; OR
In-transit metastases/satellite primary disease; OR

Single localized, primary disease meeting one of the following site-specific requirements:

Head/neck - any primary lesion if sinonasal; pT4a or above for nasal or oral cavity, given slightly improved OS
Anorectal - any primary lesion
Vaginal/cervical - any primary, as they have 5 year OS rates of 5-25
Urinary tract - any primary urethral or bladder tumor
Penile
Vulvar- AJCC cutaneous stage IIB or higher
Esophageal/gallbladder - any primary
Locoregionally recurrent following prior resection, meeting at least one of the above criteria
In addition, patients must have undergone cross-sectional imaging of the brain, chest, abdomen and pelvis with no evidence of distant metastatic disease

Disease status-Non-resected R2 or metastatic disease patients

Non-resected R2 or metastatic disease that is assessable and measurable radiographically or by physical examination

Prior Treatment:

No prior systemic checkpoint inhibitor therapy of mucosal melanoma, including in the adjuvant setting, is allowed. Prior adjuvant chemotherapy or interferon is allowed.
No other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator.
Any radiation must have completed 28 days prior to randomization and the patient must have adequately recovered from its effects.
Surgery must have completed 28 days prior to randomization.
Surgery must have completed no more than 84 days prior to randomization.
Not pregnant and not nursing, because this study has an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) >= 1,500/mm^3
Platelet count >= 100,000/mm^3
Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 50mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
Albumin >= 2.8 g/dL
Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis
Urine protein/creatinine =< 1
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

No cardiovascular disease, including:

No history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or stenting within 6 months prior to study entry.
No history of current class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system.
No refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg despite adequate attempts at anti-hypertensive therapy.
No history of myocarditis.
No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, history of Mobitz II second degree or third degree heart block without a permanent pacemaker in Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months.
No corrected QT interval by Fridericia's formula (QTcF) > 500 msec. Note: if initial QTcF is found to be > 500 ms, two additional EKGs separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard.

No underlying hematologic issues, including:

Congenital bleeding diathesis
Gastrointestinal (GI) bleeding requiring intervention within the past 6 months, unless directly related to mucosal melanoma
Active hemoptysis within 42 days prior to study enrollment.
Active tumor lesions with cavitations or tumor lesions which invade, encase, or abut major blood vessels. The anatomic location and characteristics of primary tumors or metastases as well as the medical history should be carefully reviewed in the selection of subjects for treatment with cabozantinib/placebo.
Pulmonary emboli or deep vein thromboses (DVT) that require an active anticoagulation regimen.
No known or suspected history of cytopenia (low white blood cell [WBC], hemoglobin or platelet count) of greater than 3 months duration with an unknown cause, myelodysplastic syndrome, or hematologic malignancies.
No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or viral infection requiring treatment at the time of pre-registration (e.g., active symptoms of COVID-19 infection or a post-infectious symptomatic autoimmune syndrome, serious bacterial infections requiring antibiotics).
No known or suspected gastrointestinal disorder affecting absorption of oral medications.

Comorbid conditions:

No active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
No history of autoimmune motor neuropathy (e.g., Guillain-Barre syndrome, myasthenia gravis) or non-infectious pneumonitis.
No history of severe allergic reactions to an unknown allergen or any components of the study drugs or its excipients.
No history of gastrointestinal perforation or abdominal fistula.

No clinically suspected central nervous system (CNS) (leptomeningeal or parenchymal) metastases. Patients with a history of CNS metastasis(s) will be allowed as long as

The metastatic site(s) were adequately treated as demonstrated by clinical and radiographic improvement, AND
The patient has recovered from the intervention (no residual adverse events > Common Terminology Criteria for Adverse Events [CTCAE] grade 1), AND
The patient has remained without occurrence of new or worsening CNS symptoms for a period of 28 days prior to enrollment.
No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma) within 2 years.
No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding due to liver dysfunction.
No untreated spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression. Spinal metastases must have completed planned radiation or surgical therapy prior to registration.

Concomitant medications:

Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study.
Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.

Study is for people with:

Melanoma

Phase:

Phase 2

Estimated Enrollment:

99

Study ID:

NCT05111574

Recruitment Status:

Recruiting

Sponsor:

National Cancer Institute (NCI)

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 47 Locations for this study

See Locations Near You

USC / Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States More Info
Site Public Contact
Contact
323-865-0451
Gino K. In
Principal Investigator
Saint Alphonsus Cancer Care Center-Boise
Boise Idaho, 83706, United States More Info
Site Public Contact
Contact
734-712-3671
[email protected]
John M. Schallenkamp
Principal Investigator
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell Idaho, 83605, United States More Info
Site Public Contact
Contact
734-712-3671
[email protected]
John M. Schallenkamp
Principal Investigator
Kootenai Health - Coeur d'Alene
Coeur d'Alene Idaho, 83814, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Saint Alphonsus Medical Center-Nampa
Nampa Idaho, 83686, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Kootenai Clinic Cancer Services - Post Falls
Post Falls Idaho, 83854, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Kootenai Cancer Clinic
Sandpoint Idaho, 83864, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Carle on Vermilion
Danville Illinois, 61832, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Pratima Chalasani
Principal Investigator
Carle Physician Group-Effingham
Effingham Illinois, 62401, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Pratima Chalasani
Principal Investigator
Carle Physician Group-Mattoon/Charleston
Mattoon Illinois, 61938, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Pratima Chalasani
Principal Investigator
Carle Cancer Center
Urbana Illinois, 61801, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Pratima Chalasani
Principal Investigator
Mary Greeley Medical Center
Ames Iowa, 50010, United States More Info
Site Public Contact
Contact
515-956-4132
Debra M. Prow
Principal Investigator
McFarland Clinic PC - Ames
Ames Iowa, 50010, United States More Info
Site Public Contact
Contact
515-239-4734
[email protected]
Debra M. Prow
Principal Investigator
McFarland Clinic PC-Boone
Boone Iowa, 50036, United States More Info
Site Public Contact
Contact
515-956-4132
Debra M. Prow
Principal Investigator
McFarland Clinic PC-Trinity Cancer Center
Fort Dodge Iowa, 50501, United States More Info
Site Public Contact
Contact
515-956-4132
Debra M. Prow
Principal Investigator
McFarland Clinic PC-Jefferson
Jefferson Iowa, 50129, United States More Info
Site Public Contact
Contact
515-956-4132
Debra M. Prow
Principal Investigator
McFarland Clinic PC-Marshalltown
Marshalltown Iowa, 50158, United States More Info
Site Public Contact
Contact
515-956-4132
Debra M. Prow
Principal Investigator
Bronson Battle Creek
Battle Creek Michigan, 49017, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Mercy Health Saint Mary's
Grand Rapids Michigan, 49503, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Spectrum Health at Butterworth Campus
Grand Rapids Michigan, 49503, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Bronson Methodist Hospital
Kalamazoo Michigan, 49007, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
West Michigan Cancer Center
Kalamazoo Michigan, 49007, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Ascension Borgess Cancer Center
Kalamazoo Michigan, 49009, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Mercy Health Mercy Campus
Muskegon Michigan, 49444, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores Michigan, 49444, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Spectrum Health Reed City Hospital
Reed City Michigan, 49677, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Marie Yeager Cancer Center
Saint Joseph Michigan, 49085, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Munson Medical Center
Traverse City Michigan, 49684, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Metro Health Hospital
Wyoming Michigan, 49519, United States More Info
Site Public Contact
Contact
616-391-1230
[email protected]
Kathleen J. Yost
Principal Investigator
Fairview Southdale Hospital
Edina Minnesota, 55435, United States More Info
Site Public Contact
Contact
952-993-1517
[email protected]
Daniel M. Anderson
Principal Investigator
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States More Info
Site Public Contact
Contact
855-776-0015
Robert R. McWilliams
Principal Investigator
Community Hospital of Anaconda
Anaconda Montana, 59711, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Billings Clinic Cancer Center
Billings Montana, 59101, United States More Info
Site Public Contact
Contact
800-996-2663
[email protected]
John M. Schallenkamp
Principal Investigator
Bozeman Deaconess Hospital
Bozeman Montana, 59715, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Benefis Healthcare- Sletten Cancer Institute
Great Falls Montana, 59405, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Kalispell Regional Medical Center
Kalispell Montana, 59901, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Community Medical Hospital
Missoula Montana, 59804, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Memorial Sloan Kettering Basking Ridge
Basking Ridge New Jersey, 07920, United States More Info
Site Public Contact
Contact
212-639-7592
Alexander N. Shoushtari
Principal Investigator
Memorial Sloan Kettering Westchester
Harrison New York, 10604, United States More Info
Site Public Contact
Contact
212-639-7592
Alexander N. Shoushtari
Principal Investigator
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States More Info
Site Public Contact
Contact
212-639-7592
Alexander N. Shoushtari
Principal Investigator
Cancer Centers of Southwest Oklahoma Research
Lawton Oklahoma, 73505, United States More Info
Site Public Contact
Contact
877-231-4440
Alexandra P. Ikeguchi
Principal Investigator
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States More Info
Site Public Contact
Contact
405-271-8777
[email protected]
Alexandra P. Ikeguchi
Principal Investigator
Saint Alphonsus Medical Center-Ontario
Ontario Oregon, 97914, United States More Info
Site Public Contact
Contact
406-969-6060
[email protected]
John M. Schallenkamp
Principal Investigator
Thomas Jefferson University Hospital
Philadelphia Pennsylvania, 19107, United States More Info
Site Public Contact
Contact
215-600-9151
[email protected]
Rino Seedor
Principal Investigator
HSHS Sacred Heart Hospital
Eau Claire Wisconsin, 54701, United States More Info
Site Public Contact
Contact
920-433-8889
[email protected]
Anthony J. Jaslowski
Principal Investigator
Saint Vincent Hospital Cancer Center Green Bay
Green Bay Wisconsin, 54301, United States More Info
Site Public Contact
Contact
920-433-8889
[email protected]
Anthony J. Jaslowski
Principal Investigator
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay Wisconsin, 54303, United States More Info
Site Public Contact
Contact
920-433-8889
[email protected]
Anthony J. Jaslowski
Principal Investigator
University of Wisconsin Carbone Cancer Center
Madison Wisconsin, 53792, United States More Info
Site Public Contact
Contact
800-622-8922
Vincent T. Ma
Principal Investigator
Saint Vincent Hospital Cancer Center at Oconto Falls
Oconto Falls Wisconsin, 54154, United States More Info
Site Public Contact
Contact
920-433-8889
[email protected]
Anthony J. Jaslowski
Principal Investigator
Saint Vincent Hospital Cancer Center at Sheboygan
Sheboygan Wisconsin, 53081, United States More Info
Site Public Contact
Contact
920-433-8889
[email protected]
Anthony J. Jaslowski
Principal Investigator
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay Wisconsin, 54235, United States More Info
Site Public Contact
Contact
920-433-8889
[email protected]
Anthony J. Jaslowski
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Melanoma

Phase:

Phase 2

Estimated Enrollment:

99

Study ID:

NCT05111574

Recruitment Status:

Recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.