Cabozantinib in Combination With Cetuximab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Cancer

NCT03667482 | Completed Phase 1 FDA Drug

• 1 other identifier: 18-303
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to test the safety of cabozantinib, at different doses, in combination with cetuximab to find out what effects, if any, this combined treatment has on people with HNSCC.

Conditions

Head and Neck Squamous Cell Cancer; Recurrent Head and Neck Squamous Cell Cancer; Metastatic Head and Neck Squamous Cell Cancer

Keywords

Cabozantinib; Cetuximab; 18-303

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD)

  from 3 testing dose levels: 20, 40, and 60. Three patients will be enrolled at the dose level 0 of 40 mg. The dose escalation scheme is as follows: 1. If none of the initial three patients at a given dose level experience DLT within 4 weeks, the next dose level will be studied. 2. If one of the initial three patients at a given dose level experiences DLT, three additional patients will be treated at the same dose level. Escalation will continue only if there is no additional DLT observed.If two or more patients experience DLT at a given dose, the previous dose level will be studied. Should two or more patients experience the DLT at the lowest dose level (20 mg), the study will be halted, and alternative dosing will be considered. 4\. The highest dose level with no more than one DLT among six patients will be declared as the MTD. If only three patients were treated at a dose under consideration as the MTD, an additional three patients will be treated at that level.

  2 years

Study Arms (1)

Cabozantinib in Combination With Cetuximab

EXPERIMENTAL

Cetuximab will be administered at 500 mg/m\^2 intravenously every other week. Cabozantinib will be initiated at 40 mg PO daily, with subsequent 20 mg or 40 mg doses as tolerated per the study design.

Drug: Cabozantinib; Drug: Cetuximab

Interventions

Cabozantinib DRUG

Cabozantinib will be initiated at 40 mg PO daily, with subsequent 20 mg or 40 mg doses as tolerated per the study design.

Cabozantinib in Combination With Cetuximab

Cetuximab DRUG

Cetuximab will be administered at 500 mg/m\^2 intravenously every other week on Days 1 and 15 of each cycle, with a window of up to 3 days before the scheduled date. In an effort to prevent a hypersensitivity reaction, it is recommended that all patients pre-medications, hydration, and anti-emetics will be given according to institutional guidelines and/or per treating physician discretion.

Cabozantinib in Combination With Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who meet each of the following criteria will be considered "eligible":
• Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck.
• Disease must be considered incurable. Incurable is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection).
• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm with CT scan, as \>20 mm by chest x-ray, or \>10 mm with calipers by clinical exam.
• Patients may have received pembrolizumab, platins, cetuximab or other chemotherapies in the metastatic setting, but do not need to have received cetuximab.
• Measurable disease per RECIST v1.1 as determined by the investigator;
• The subject has had an assessment of all known disease sites e.g., by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate, within 28 days before the first dose of cabozantinib.
• A CT of the neck and a CT of the chest will be required at baseline for all patients.
• The subject is ≥ 18 years old on the day of consent.
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Recovery to baseline or ≤ Grade 1 CTCAE v.5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• The subject has organ and marrow function and laboratory values as follows within 14 days before the first dose of cabozantinib.
• The ANC ≥ 1500/mm3 without colony stimulating factor support.
• White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L).
• Platelets ≥ 100,000/mm3;

You may not qualify if:

• Patients who meet any of the following criteria will be considered "ineligible":
• Any patient who has received \>70 Gy of XRT to the neck in the same radiation field. No head and neck radiation within 2 months prior to initiation. Treatment areas should be healed with no sequelae from RT that would predispose to fistula formation.
• A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, synchronous H\&N primaries or low grade tumors deemed cured and not treated with systemic therapy. Other cancers that will not affect the study outcome may be included with the consent of the PI (Dr. Michel) as long as it would not affect the study outcome (e.g., low grade prostate cancer on surveillance alone).
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment with the exception of cetuximab and small molecule kinase inhibitors (kinase inhibitors must be stopped within 2 weeks of first dose of study treatment.
• Prior treatment with cabozantinib.
• Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.;
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment. Note: Subjects with prostate cancer currently receiving LHRH or GnRH agonists may be maintained on these agents.
• The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment.
• The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment.
• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel).
• Allowed anticoagulants are the following:
• Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
• Low-dose low molecular weight heparins (LMWH) are permitted.
• Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (9)

Baptist Alliance MCI

Miami, Florida, 33143, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

cabozantinib; Cetuximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Loren Michel, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A standard 3+3 design will be used to find the maximum tolerated dose (MTD) from 3 testing dose levels: 20, 40, and 60.

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: September 12, 2018
• Study Start: September 7, 2018
• Primary Completion: July 17, 2024
• Study Completion: July 17, 2024
• Last Updated: July 23, 2024

Record last verified: 2024-07

Locations

US (9)