Afatinib and Nivolumab as Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

NCT03652233 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: VICC HN 1840NCI-2018-01790
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I/Ib trial will assess the dose, safety and side effects of the combination of the cancer drugs afatinib (GILOTRIF®) and nivolumab (OPDIVO®) and to assess the anti-cancer effects of this combination of drugs when used to treat patients with advanced head and neck cancers that did not respond to previous treatments.

Conditions

Recurrent Squamous Cell Carcinoma of the Head or Neck; Metastatic Squamous Cell Carcinoma of the Head or Neck; Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (phase I)

  Up to 42 days

• Dose limiting toxicities (phase I)

  Up to 42 days

• Number of participants with treatment-related adverse events as assessed by CTCAE version 4.0

  Up to 24 months

Secondary Outcomes (3)

• Progression free survival

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

• Overall survival

  From date of enrollment to date of death from any cause assessed up to 3 years.

• Objective response rate

  Up to 24 months

Study Arms (1)

Afatinib and Nivolumab

EXPERIMENTAL

Drug: Nivolumab; Drug: Afatinib

Interventions

Nivolumab DRUG

Given by vein every 14 days for up to 12 months

Afatinib and Nivolumab

Afatinib DRUG

Taken by mouth daily for up to 12 months

Afatinib and Nivolumab

Eligibility Criteria

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

You may qualify if:

• Recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy
• No prior immunotherapy for this disease, including therapies targeting PD-
• , PD-L1, CTLA-4 or other cells and molecules aiming to modulate immune response against Squamous Cell Carcinoma of the Head and Neck.
• ECOG Performance Status of 0-1
• Normal organ and marrow function as defined below:
• WBC ≥ 2000 cells/μL
• Absolute neutrophil count (ANC) ≥ 1000 cells/μL
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets ≥ 100,000/μL
• Estimated creatinine clearance ≥ 30 ml/min
• Left ventricular function with resting ejection fraction ≥ 50%
• Total bilirubin \< 1.5 X ULN (Subjects with Gilbert's syndrome total bilirubin must be ≤4 times institutional upper limit of normal)
• AST and ALT of \< 2.5 X ULN
• Ability to understand and the willingness to sign a written informed consent document.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of Nivolumab. WOCBP must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.

You may not qualify if:

• Currently receiving any other investigational agents or using an investigational agent 30 days prior to the first dose of trial treatment.
• Disease that is suitable for local therapy with curative intent.
• Untreated brain metastases/CNS disease excluded because of poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Subjects with stable, treated CNS metastases are eligible.
• Known hypersensitivity to afatinib or nivolumab.
• Prior EGFR-targeted small molecule therapy except cetuximab.
• Hormonal therapy with the exception of those used for diabetes or birth control is not allowed.
• Radiotherapy within 4 weeks prior to randomization, except as follows:
• Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior to randomisation, and Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.
• Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study.
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension (systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 90), congestive heart failure NYHA classification of ≥ 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to the enrollment.
• Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
• Requiring treatment with any of the prohibited concomitant medications listed in section 6.4 that cannot be stopped for the duration of trial participation.
• Known active or pre-existing interstitial lung disease.
• Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea and malabsorption).
• Prior immune checkpoint targeted therapy, including anti-PD-1, anti-PD-L1 or anti-PD-L2.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Comprehensive Cancer Network: collaborator
• Boehringer Ingelheim: collaborator

MeSH Terms

Conditions

Carcinoma, Squamous Cell

Interventions

Nivolumab; Afatinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mike Gibson, MD, PhD

  Vanderbilt-Ingram 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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 29, 2018
• Study Start: November 2, 2018
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2022
• Last Updated: June 20, 2019

Record last verified: 2019-06