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BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study

ConditionsClinical Stage III Cutaneous Melanoma AJCC v8Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Clinical Stage IV Cutaneous Melanoma AJCC v8Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Locally Recurrent Head and Neck Squamous Cell CarcinomaLocally Recurrent Hypopharyngeal Squamous Cell CarcinomaLocally Recurrent Laryngeal Squamous Cell CarcinomaLocally Recurrent Oral Cavity Squamous Cell CarcinomaLocally Recurrent Oropharyngeal Squamous Cell CarcinomaMetastatic Head and Neck Squamous Cell CarcinomaMetastatic Hypopharyngeal Squamous Cell CarcinomaMetastatic Laryngeal Squamous Cell CarcinomaMetastatic MelanomaMetastatic Oral Cavity Squamous Cell CarcinomaMetastatic Oropharyngeal Squamous Cell CarcinomaRecurrent MelanomaStage III Hypopharyngeal Carcinoma AJCC v8Stage III Laryngeal Cancer AJCC v8Stage III Lip and Oral Cavity Cancer AJCC v8Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8Stage IV Hypopharyngeal Carcinoma AJCC v8Stage IV Laryngeal Cancer AJCC v8Stage IV Lip and Oral Cavity Cancer AJCC v8Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8Unresectable Melanoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). 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, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are "tumor mutational burden" and "tumor inflammation signature." Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

STEP 1 - SPECIMEN SUBMISSION

Participants must have histologically confirmed melanoma that is stage III or IV, unresectable, recurrent, or metastatic non-uveal melanoma OR Participants must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) that is either locally recurrent and non-amendable to curative therapy (e.g., radiation, surgery) or metastatic. The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible

Note: For participants with primary oropharyngeal cancer, human papillomavirus (HPV) or p16 status must be known prior to step 1 registration

Participants must have disease presentation consistent with measurable disease. Note: Current disease measurements will not be required until step 2 registration

Disqualifiers

None

Trial design

Design model

Single group

Treatments tested in this trial

  • Biopsy Procedure

    Procedure/Surgery

    Undergo tumor biopsies

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Cabozantinib S-malate

    Drug

    Given PO

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scans

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI scans

  • Nivolumab

    Biological/Vaccine

    Given IV

Treatment groups

150 Participants
are divided into 1 treatment group
Group A: Treatment (nivolumab and cabozantinib)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

Biomarker results turnaround time

A biomarker turnaround time estimate of at least 75% less than or equal to 21 days will be considered successful with respect to feasibility. For melanoma participants prior to Revision #7, turnaround time is defined as the time-period between date of tissue submission by the site to central repository and date the site was sent notification of participant molecular group determination. For head and neck squamous cell carcinoma (HNSCC) and melanoma participants after Revision #7, turnaround time is defined as the time-period between date of tissue submission by the site to central repository and one day after results have been received from the initial tissue submission by the Southwest Oncology Group Statistics and Data Management Center to simulate when the site would have received notification of participant molecular group determination.

Time frame
Up to 21 days
2

Objective response rate

Confirmed and unconfirmed complete and partial responses in tumor inflammation score subgroups. Will assess biomarker response association. To test this association, will consider combination of biomarkers coded as 0 = Lo/Lo, 1 = Lo/Hi or Hi/Lo, and 2 = Hi/Hi. Assume each biomarker level is associated with an odds-ratio of approximately 3.1 (for example, corresponding to a difference in response rate of 5 percent to 14 percent from Lo/Lo to Lo/Hi or Hi/Lo). For the melanoma cohort, with approximately equal sized biomarker combination subgroups, a one-sided 0.10 level test for trend using (0,1,2) coding with logistic regression has a power of 80%. The same analysis for HNSCC will have lower power for the same effect size due to the unequal frequencies in the subgroups defined by the biomarkers. We will also conduct disease-by-biomarker interaction tests; however, there will be limited power to detect even to detect relatively large interaction parameters.

Time frame
At the end of stage I

Secondary outcomes

1

Rate and profile of >= grade 3 treatment-related adverse events

Per Common Terminology Criteria for Adverse Events 5.0. With respect to overall disease group, 60 participants are sufficient to estimate the probability of a particular toxicity to within +/- 13 percent. Any toxicity occurring with at least a 5 percent probability is likely to be seen at least once (95 percent chance).

Time frame
Up to 2 years
2

Disease control rate

Will be estimated using the method of Kaplan-Meier.

Time frame
Up to 2 years
3

Progression-free survival

Will be estimated using the method of Kaplan-Meier.

Time frame
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years
4

Overall survival

Will be estimated using the method of Kaplan-Meier.

Time frame
From date of registration to date of death due to any cause, assessed up to 2 years

Other outcomes

1

Additional markers of response or resistance

Explore additional markers of response or resistance through hypothesis generating analysis. Tumor mutational burden (TMB) will be evaluated as an exploratory biomarker within each disease cohort. Both the binary cut-point of TMB high/low will be considered as well as TMB as a continuous variable (including log-transformed) will be assessed in a logistic regression model.

Time frame
Up to 2 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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