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Recurrent Squamous Cell Carcinoma of the Head or NeckPhase 1NCT03652233

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

A Phase 1 study testing Nivolumab and Afatinib in people with Recurrent Squamous Cell Carcinoma of the Head or Neck and Metastatic Squamous Cell Carcinoma of the Head or Neck, run by Vanderbilt-Ingram Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab and Afatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
2 Nov 2018to Nov 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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-
  • 1, 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
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  • 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.
  • Recovered from any previous therapy related toxicity to ≤ Grade 1 at study entry (except for stable sensory neuropathy ≤ Grade 2 and alopecia).
  • Availability of a "newly obtained" standard of care biopsy obtained through either core or excisional biopsy. A newly obtained sample may be obtained up to 28 days prior to treatment initiation. Tissue beyond the 28-day window may be considered with the approval Protocol Chair. Tissue that has been previously irradiated or surgically intervened is acceptable

Who cannot join

  • 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.
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  • 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.
  • History of autoimmune disease or disease requiring immunosuppression therapy.
  • Uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Women must not be breastfeeding.
  • Men who are sexually active with WOCBP must use any contraceptive method (Appendix II) with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
  • Testing positive Human Immunodeficiency Virus (HIV) acquired immunodeficiency syndrome (AIDS).
  • Active hepatitis B or hepatitis C.
  • Active infection requiring systemic antibiotic treatment or intensive care.
  • Active non-infectious pneumonitis
  • Received live vaccine within 30 days of start of study treatment.
  • Known psychiatric or substance abuse disorders that may interfere with cooperation with the requirements of the trial.
  • Other significant medical conditions that may interfere with surgical biopsy and afatinib and nivolumab administration.

About this study

Official title: Afatinib and Nivolumab for Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Not Previously Treated With Immunotherapy.

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.

Read the detailed description

Primary Objectives:

Phase I: To determine dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of afatinib when given in combination with nivolumab for subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy

Phase IB: To determine long term safety of afatinib in combination with nivolumab when administered to subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck who had experienced disease progression during or after platinum- and cetuximab-based chemotherapy regimen.

Secondary Objectives:

To assess progression free survival and overall survival of afatinib in combination with nivolumab when given to subjects with recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy.

To estimate HPV stratified ORR as assessed by irRECIST in recurrent/metastatic Squamous Cell Carcinoma of the Head and Neck not previously treated with immunotherapy.

Exploratory Objectives:

  • Determination of key molecular alterations that may confer treatment resistance. Specifically, we will examine key somatic mutations in ERBB1 (exons 18-21), ERBB2 (exon 20), and BRAF (V600) genes. We will further characterize the expression levels of ErbB2 and phosphatase and tensin homolog (PTEN) in tumor samples.
  • Characterization of active CD8+ T-cell density and PD-L1 expression levels in the tumor parenchyma pre- and on-treatment. Immunogenicity will be assessed by expression and localization of key molecules PD-1, PD-L1, CTLA-4, TIM-3, LAG-3 and OX40 within the tumor parenchyma.
  • Characterization of circulating monocytic myeloid-derived suppressor cells (m-MDSCs) frequency from pre-treatment peripheral blood samples.
  • Characterization of HBD3 expression in the tumor parenchyma from pre-treatment tumor tissue samples.
Being tested
Nivolumab, Afatinib
Medical subject headings
Carcinoma, Squamous Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Given by vein every 14 days for up to 12 months

  • AfatinibDrug

    Taken by mouth daily for up to 12 months

Study groups in NCT03652233
Study groupRoleWhat they receive
Afatinib and NivolumabExperimentalNot described
Receives: Drug: Nivolumab; Drug: Afatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (phase I)

    Measured: Up to 42 days

  2. Dose limiting toxicities (phase I)

    Measured: Up to 42 days

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

    Measured: Up to 24 months

Secondary outcomes (3)

  1. Progression free survival

    Measured: 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

  2. Overall survival

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

  3. Objective response rate

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2018
  2. Study start2 Nov 2018
  3. Primary completionNov 2021 (estimated)
  4. Study completionNov 2022 (estimated)

Why it stopped: Low accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03652233
Sponsor's protocol ID
VICC HN 1840
Other IDs
NCI-2018-01790
Status last verified
Jun 2019
First submitted
20 Aug 2018
Last updated
20 Jun 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nivolumab and Afatinib in people with Recurrent Squamous Cell Carcinoma of the Head or Neck and Metastatic Squamous Cell Carcinoma of the Head or Neck, run by Vanderbilt-Ingram Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 20 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (phase I) (time frame: Up to 42 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03652233.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2019.

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