We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    s2101
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05136196
Recruitment Status : Recruiting
First Posted : November 29, 2021
Last Update Posted : February 3, 2023
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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 has spread to other places in 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.

Condition or disease Intervention/treatment Phase
Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Locally Recurrent Head and Neck Squamous Cell Carcinoma Metastatic Cutaneous Melanoma Metastatic Head and Neck Squamous Cell Carcinoma Metastatic Hypopharyngeal Squamous Cell Carcinoma Metastatic Laryngeal Squamous Cell Carcinoma Metastatic Oral Cavity Squamous Cell Carcinoma Metastatic Oropharyngeal Squamous Cell Carcinoma Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 Pathologic Stage IIID Cutaneous Melanoma AJCC v8 Pathologic Stage IV Cutaneous Melanoma AJCC v8 Recurrent Cutaneous Melanoma Recurrent Hypopharyngeal Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Oral Cavity Squamous Cell Carcinoma Recurrent Oropharyngeal Squamous Cell Carcinoma Stage III Hypopharyngeal Carcinoma AJCC v8 Stage III Laryngeal Cancer AJCC v8 Stage III Lip and Oral Cavity Cancer AJCC v8 Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage IV Hypopharyngeal Carcinoma AJCC v8 Stage IV Laryngeal Cancer AJCC v8 Stage IV Lip and Oral Cavity Cancer AJCC v8 Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Unresectable Cutaneous Melanoma Procedure: Biopsy Procedure: Biospecimen Collection Drug: Cabozantinib S-malate Procedure: Computed Tomography Procedure: Magnetic Resonance Imaging Biological: Nivolumab Phase 2

Show Show detailed description
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Biomarker Stratified CaboZantinib (NSC#761968) and NivOlumab (NSC#748726) (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Patients With Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study
Actual Study Start Date : October 14, 2022
Estimated Primary Completion Date : March 15, 2025
Estimated Study Completion Date : October 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Treatment (nivolumab and cabozantinib)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and cabozantinib PO BID. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans and collection of blood samples throughout the trial. Patients undergo a tumor biopsy during screening and optionally during follow-up.
 Procedure: Biopsy
Undergo tumor biopsies
Other Names:
  • BIOPSY_TYPE
  • Bx

Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Drug: Cabozantinib S-malate
Given PO
Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184

Procedure: Computed Tomography
Undergo CT scans
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography

Procedure: Magnetic Resonance Imaging
Undergo MRI scans
Other Names:
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Biomarker results turnaround time [ Time Frame: 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, assessed within 21 days ]
    A biomarker turnaround time estimate of at least 75% within 21 days will be considered successful with respect to feasibility.

  2. Objective response rate [ Time Frame: At the end of stage I ]
    Confirmed and unconfirmed complete and partial responses) in molecular subgroups. 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). A one-sided .10 level test for trend using (0,1,2) coding above with logistic regression has a power of 80 percent. We will also consider biomarker trend analysis adjusting for disease types. We will also conduct disease-by-biomarker interaction tests; however, there will be limited power even to detect relatively large interaction parameters.


Secondary Outcome Measures :
  1. Rate and profile of >= grade 3 treatment-related adverse events (TRAE) [ Time Frame: Up to 2 years ]
    Per Common Terminology Criteria for Adverse Events (CTCAE) 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).

  2. Disease control rate (DCR) [ Time Frame: Up to 2 years ]
    Will be estimated using the method of Kaplan-Meier.

  3. Progression-free survival (PFS) [ 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 ]
    Will be estimated using the method of Kaplan-Meier.

  4. Overall survival (OS) [ Time Frame: From date of registration to date of death due to any cause, assessed up to 2 years ]
    Will be estimated using the method of Kaplan-Meier.

  5. Turnaround time for the Tumor Inflammation Score (TIS) in stage I [ Time Frame: Assessed within 21 days ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • STEP 1 - SPECIMEN SUBMISSION INCLUSION CRITERIA

  • 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
  • Participants must have had documented progression within 12 weeks after the last dose of PD-1 checkpoint inhibition-based therapy. Participants must have been receiving checkpoint inhibition for a minimum of 6 weeks prior to progression. Participants who recur during adjuvant anti-PD1 treatment or within 12 weeks of completion of adjuvant anti-PD1 treatment are eligible if they have measurable disease and considered unresectable
  • Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test within 6 months prior to step 1 registration
  • Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to step 1 registration
  • Participants with a history of hepatitis C virus (HCV) infection must have no detectable viral load within 28 days prior to step 1 registration
  • Participants must have recovered to baseline or =< Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 toxicities related to any prior treatments, unless adverse events are deemed clinically nonsignificant by the treating investigator or stable on supportive therapy
  • Participants must be >= 18 years of age
  • Participants must have a Zubrod Performance Status 0 or 1
  • Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better to be eligible for this trial
  • Have adequate tissue specimen from procedure obtained within 6 months prior to step 1 registration and after development of resistance to anti-PD-1/L1 therapy. Archival tissue must consist of tumor block or at least 20 freshly cut serially sectioned and numbered 4-5 micron unstained, positively-uncharged slides OR

Be willing to undergo research biopsy AND have tumor accessible for biopsy based on the following criteria:

  • Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies can be obtained incidentally to a clinically necessary procedure and NOT for the sole purpose of the clinical trial

  • Acceptable biopsy procedures are:

    • Percutaneous biopsy with local anesthetic and/or sedation with an expected risk of severe complications < 2%
    • Direct transoral biopsy (with or without local anesthetic and/or sedation) with an expected risk of severe complications < 2%
    • Excisional cutaneous biopsy with local anesthetic and/or sedation with an expected risk of severe complications < 2%
    • Biopsy with removal of additional tumor tissue during a medically necessary mediastinoscopy, laparoscopy, gastrointestinal endoscopy, bronchoscopy or craniotomy. No open surgical, laparoscopic or endoscopic procedure should be performed solely to obtain a biopsy for this protocol

    • Removal of additional tumor tissue during a medically necessary surgical procedure

      • Participants must have been offered the opportunity to participate in specimen banking
      • Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

  • Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)

    • STEP 2 TREATMENT REGISTRATION INCLUSION CRITERIA
    • Participants must have been eligible for step 1 registration
    • Participants must have had their tumor tissue submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System prior to step 2 registration
    • Participants registered during stage II of the protocol must have received assignment to an open cohort from the SWOG Statistics and Data Management Center based on their biomarker screening profile (not applicable for patients registered during stage I of the protocol)
    • Participants must have measurable disease. All measurable disease must be assessed within 28 days prior to step 2 registration. All non-measurable disease must be assessed within 42 days prior to step 2 registration. Note: All disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
    • For melanoma participants, computed tomography (CT) chest, abdomen and pelvis must be obtained. For HNSCC participants, CT neck and chest must be obtained. Further imaging (i.e., magnetic resonance imaging [MR] brain, CT abdomen/pelvis or extremities, bone scan) will be performed as deemed appropriate by the treating physician
    • Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy
    • Participants with treated brain metastases must have discontinued steroid treatment at least 14 days prior to step 2 registration
    • Participants must have a history and physical examination performed within 28 days prior to step 2 registration
    • Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules
    • Leukocytes >= 3,000/uL (within 28 days prior to step 2 registration)
    • Absolute neutrophil count >= 1,500/uL (within 28 days prior to step 2 registration)
    • Platelets >= 100,000/uL (within 28 days prior to step 2 registration)
    • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) or =< 3 x ULN for participants with Gilbert's disease (within 28 days prior to step 2 registration)
    • Aspartate aminotransferase (AST) =< 3 x institutional ULN (within 28 days prior to step 2 registration)
    • Alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to step 2 registration)
    • Urinalysis: For baseline value (no required value for eligibility)
    • Fridericia corrected QT interval (QTcF) =< 470 milliseconds on screening electrocardiogram (ECG) (within 28 days prior to step 2 registration)
    • Creatinine =< 3 x institutional ULN OR measured (OR calculated) creatinine clearance >= 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to Step 2 registration

Exclusion Criteria:

  • STEP 1 - SPECIMEN SUBMISSION EXCLUSION CRITERIA
  • Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV as mentioned above)
  • Participants must not have received surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to step 1 registration

  • Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the head and neck, with the additional following criteria:

    • If the primary radiation is combined with chemotherapy, a minimum of 16 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration. If the radiation is given alone, a minimum of 8 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration
    • Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) and must be completed at least 4 weeks prior to step 1 registration
    • Treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation
  • Participants must not have received prior treatment with anti-VEGF therapies for any reason
  • Participants must not have any known significant organ disfunction that, in the opinion of the treating investigator, may impact suitability for receiving combination nivolumab/cabozantinib treatment

  • Participants must not have active autoimmune disease requiring systemic steroids (equivalent of > 10mg of prednisone) or other immune suppression. Exceptions:

    • Type 1 diabetes mellitus
    • Hypothyroidism only requiring hormone replacement
    • Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment
    • Conditions not expected to recur in the absence of an external trigger
  • Participants must not have received an organ allograft
  • Participants must not have a history of hemoptysis (defined as >= 1/2 tsp of bright red blood per day) or tumor bleeding within 90 days prior to step 1 registration
  • Participants must not have known central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (e.g., carotid artery)

  • Participants must not require concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)

    • Participants must not require anticoagulants except for the following:

      • Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
      • Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors, rivaroxaban, edoxaban, or apixaban in participants without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to step 1 registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
  • Participants must not have evidence of preexisting uncontrolled hypertension prior to step 1 registration as documented by 2 baseline blood pressure readings taken at least 30 minutes apart within 28 days prior to step 1 registration. The baseline systolic blood pressure readings must be =< 150 mmHg and the baseline diastolic blood pressure readings must be =< 90 mmHg. Participants on antihypertensive therapies with controlled blood pressure are eligible
  • Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • Participants must not be pregnant or nursing due to the known safety profiles of the drugs in this study. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential. In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion and vasectomy with testing showing no sperm in the semen
  • STEP 2 TREATMENT REGISTRATION EXCLUSION CRITERIA
  • Participants must not have experienced any significant health changes that, in the opinion of the treating investigator, may impact continued suitability for receiving combination nivolumab/cabozantinib treatment

  • Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the head and neck, with the additional following conditions:

    • If the primary radiation is combined with chemotherapy, a minimum of 16 weeks will be required to have elapsed between the end of radiotherapy and step 2 registration. If the radiation is given alone, a minimum of 8 weeks will be required to have elapsed between the end of radiotherapy and step 2 registration
    • Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) and must be completed at least 4 weeks prior to step 2 registration
    • Treatment areas should be healed with no sequelae from RT that would predispose to fistula formation
  • Participants must not have received investigational agents or monoclonal antibodies (except Food and Drug Administration [FDA] approved supportive care antibodies, such as denosumab) within 28 days prior to step 2 registration
  • Participants must not have received any prior treatment with anti-VEGF based therapies
  • Participants must not have received administration of a live, attenuated vaccine within 30 days prior to step 2 registration. Note: Participants may have received a messenger ribonucleic acid (mRNA) or viral vector-based COVID-19 vaccine within 30 days prior to step 2 registration
  • Participants must not have received administration of any strong CYP3A4 inducers, such as but not limited to rifampin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John's wort, within 14 days prior to step 2 registration
  • Participants must not have received administration of any strong CYP3A4 inhibitors, such as but not limited to clarithromycin, itraconazole, ketoconazole, grapefruit juice, indinavir, nelfinavir, ritonavir, nefazodone, saquinavir, and telithromycin, within 5 times the half-life of the CYP3A inhibitor prior to step 2 registration
  • Participants must not have malabsorption syndrome
  • Participants must not have central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (e.g., carotid artery)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05136196


Locations
Show Show 53 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Siwen Hu-Lieskovan Southwest Oncology Group
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT05136196    
Other Study ID Numbers: NCI-2021-12653
NCI-2021-12653 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S2101 ( Other Identifier: SWOG )
S2101 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
First Posted: November 29, 2021    Key Record Dates
Last Update Posted: February 3, 2023
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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
URL: https://grants.nih.gov/policy/sharing.htm

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Melanoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Skin Neoplasms
Laryngeal Neoplasms
Mouth Neoplasms
Oropharyngeal Neoplasms
Lip Neoplasms
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
 Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Skin Diseases
Otorhinolaryngologic Neoplasms
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Mouth Diseases