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

Sponsor:

Collaborators:

Information provided by (Responsible Party):

，

Tracking Information

First Submitted Date ^ICMJE

October 1, 2018

First Posted Date ^ICMJE

October 4, 2018

Last Update Posted Date

October 4, 2018

Actual Study Start Date ^ICMJE

November 2018

Estimated Primary Completion Date

April 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Objective response rate[ Time Frame: 2 years ]

The objective response rate will be measured by RECIST 1.1.

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Overall survival[ Time Frame: 2 years ]
Overall survival: from the start of study treatment, to the time of death Progression free survival: from the start of study treatment, to the time of disease progression (RECIST 1.1) or death.
Toxicities[ Time Frame: 2 years ]
CTCAE 4.0, Grade 3 or higher

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma, A Single-Arm, Phase II Study (ALPHA Study)

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.

Detailed Description

It is a single arm, phase II, single center, prospective, open label clinical trial.

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation:
Intervention Model: Single Group Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: Afatinib Oral Tablet
40mg oral, daily, continuously
Drug: Pembrolizumab Injection
200mg, intra-venous injection, every 3 weeks, for 35 cycles

Study Arms

Experimental: Study arm
afatinib + pembrolizumab

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

April 2021

Estimated Primary Completion Date

April 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion criteria 1. Histologically confirmed squamous cell carcinoma of oral cavity, oropharynx, hypopharynx, or larynx. 2. 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. 3. 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. 4. 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. 5. Age ≥ 20 years 6. ECOG performance status: ≤ 2 7. Adequate organ function 8. Recovered from any previous therapy related toxicity to ≤Grade 1 at study entry (except for stable sensory neuropathy ≤Grade 2 and alopecia) 9. Agree to take biopsy before and during the treatment 10. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 11. 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. 12. 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. 13. 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. 3.3.3 Exclusion criteria 1. Nasopharyngeal carcinoma or nasal cavity malignancies other than HNSCC 2. Concurrent malignancies other than HNSCC 3. Prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, or other immune checkpoint inhibitors 4. Prior exposure to gefitinib, erlotinib, afatinib, osimertinib, or other known EGFR TKI inhibitors 5. 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. 6. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 7. Has an active infection requiring systemic therapy 14 days before signing informed consent. 8. 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. 9. Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study. 10. 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. 11. Has known history of pneumonitis requiring steroids, or any evidence of active, non-infectious pneumonitis, or other known interstitial lung disease 12. 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. 13. 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. 14. 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. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 16. Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug 17. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 18. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. 19. 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 diarrhoea, malabsorption)

Sex/Gender

Sexes Eligible for Study:

All

Ages

20 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Taiwan

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

National Taiwan University Hospital

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator: Ruey-Long Hong, MD PhD Department of Oncology, National Taiwan University Hospital

PRS Account

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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