Afatinib and Pembrolizumab for Head and Neck Squamous Cell Carcinoma (ALPHA Study)

NCT03695510 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 201803071MIPD
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of the trial is to examine the toxicities and efficacies of afatinib and pembrolizumab for recurrent and/or metastatic head and neck squamous cell carcinoma.

Conditions

Head and Neck Neoplasms

Keywords

head and neck cancer,Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  The objective response rate will be measured by RECIST 1.1.

  2 years

Secondary Outcomes (2)

• Overall survival

  2 years

• Toxicities

  2 years

Study Arms (1)

Study arm

EXPERIMENTAL

afatinib + pembrolizumab

Drug: Afatinib Oral Tablet; Drug: Pembrolizumab Injection

Interventions

Afatinib Oral Tablet DRUG

40mg oral, daily, continuously

Also known as: Giotrif

Study arm

Pembrolizumab Injection DRUG

200mg, intra-venous injection, every 3 weeks, for 35 cycles

Also known as: Keytruda

Study arm

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed squamous cell carcinoma of oral cavity, oropharynx, hypopharynx, or larynx.
• The recurrent disease is not suitable for curative surgery or definitive chemoradiation, and/or metastatic diseases which are not amenable to surgery and/or curative radiotherapy.
• Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting. Clinical progression after platinum therapy is an allowable event for entry and is defined as progression of a lesion at least 10 mm in size that is amenable to caliper measurement (eg superficial skin lesion as per RECIST 1.1) or a lesion that has been visualized and photographically recorded with measurements and shown to have progressed.
• Measurable disease according to RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Age ≥ 20 years
• ECOG performance status: ≤ 2
• Adequate organ function
• Recovered from any previous therapy related toxicity to ≤Grade 1 at study entry (except for stable sensory neuropathy ≤Grade 2 and alopecia)
• Agree to take biopsy before and during the treatment
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Female subject of childbearing potential should have a negative urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 60 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 150 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Nasopharyngeal carcinoma or nasal cavity malignancies other than HNSCC
• Concurrent malignancies other than HNSCC
• Prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, or other immune checkpoint inhibitors
• Prior exposure to gefitinib, erlotinib, afatinib, osimertinib, or other known EGFR TKI inhibitors
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as positive anti-HCV) infection.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has an active infection requiring systemic therapy 14 days before signing informed consent.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• 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, 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 randomisation.
• Has known history of pneumonitis requiring steroids, or any evidence of active, non-infectious pneumonitis, or other known interstitial lung disease
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Topical or inhaled steroids is not considered as systemic treatment.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (1)

• Kao HF, Liao BC, Huang YL, Huang HC, Chen CN, Chen TC, Hong YJ, Chan CY, Chia JS, Hong RL. Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (ALPHA Study): A Phase II Study with Biomarker Analysis. Clin Cancer Res. 2022 Apr 14;28(8):1560-1571. doi: 10.1158/1078-0432.CCR-21-3025.

  PMID: 35046059 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Afatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ruey-Long Hong, MD PhD

  Department of Oncology, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: October 4, 2018
• Study Start: January 24, 2019
• Primary Completion: April 14, 2022
• Study Completion: April 14, 2022
• Last Updated: April 21, 2022

Record last verified: 2022-04

Locations

TW (1)