Alpelisib in Treating Participants With Transorally Resectable HPV-Associated Stage I-IVA Oropharyngeal Cancer

NCT03601507 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: 1802258478NCI-2018-00507CBYL719XUS15TP30CA023074
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well alpelisib works in treating participants with human papillomavirus(HPV)-associated stage I-IVA head and neck cancer that can be removed by surgery. Alpelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

CDKN2A-p16 Positive; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma AJCC V7; Stage II Oropharyngeal Squamous Cell Carcinoma AJCC V7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7

Outcome Measures

Primary Outcomes (2)

• Quantitative Change in the Sum of Response Evaluation Criteria in Solid Tumors (RECIST) -

  Measurable index lesions on paired, pre-and post-treatment computed tomography scans (delta change in T) with size treated as a continuous variable. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD) is the sum of target lesions have increased by \>=20% and \>=5 mm from nadir; Stable disease (SD) neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  Baseline up to 28 days

• Percent Change in Tumor Size (Change in T) in Patients With Genomic PIK3CA Pathway Alteration (PIK3CA Mutation, Amplification, and Fluorescence in Situ Hybridization [FISH] for PTEN Loss)

  Will compare percent change in tumor size (change in T) in patients with genomic PIK3CA pathway alteration (PIK3CA mutation, amplification, and fluorescence in situ hybridization \[FISH\] for PTEN loss) versus no genomic activation.

  Baseline up to 28 days

Secondary Outcomes (7)

• Percentage of Participants With Adverse Events

  Baseline up to 28 days

• Surgical Complications

  Baseline up to 28 days

• Length of Hospital Stay

  Baseline up to 28 days

• Changes in Pre- and Post-treatment Tumor Levels of Human Papillomavirus (HPV) Messenger Ribonucleic Acid (mRNA) (Quantitative Polymerase Chain Reaction [qPCR])

  Baseline up to 28 days

• Changes in Pre- and Post-treatment Tumor Levels of E6 and E7 Oncoproteins

  Baseline up to 28 days

Study Arms (1)

Treatment (Alpelisib)

EXPERIMENTAL

Participants receive Alpelisib PO QD for 14-21 days in the absence of disease progression of unacceptable toxicity and then undergo surgery. Participants may receive Alpelisib for up to 28 days if surgery is delayed.

Drug: Alpelisib; Other: Laboratory Biomarker Analysis; Other: Pharmacodynamic Study; Procedure: Therapeutic Conventional Surgery

Interventions

Alpelisib DRUG

Given PO

Also known as: BYL719, Phosphoinositide 3-kinase Inhibitor BYL719

Treatment (Alpelisib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Alpelisib)

Pharmacodynamic Study OTHER

Correlative studies

Also known as: PHARMACODYNAMIC

Treatment (Alpelisib)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (Alpelisib)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytologic or histologic diagnosis of p16+ squamous cell carcinoma of oropharyngeal or unknown primary metastatic to the cervical met.
• p16 positivity is defined as ≥70% of tumor cells demonstrating diffuse cytoplasmic and nuclear staining for p16 by immunohistochemistry in a CLIA certified pathology lab.
• Clinical stage I-IVa p16+ oropharyngeal squamous cell carcinoma, based upon the AJCC staging manual, 7th edition.
• No evidence of distant metastatic disease.
• Appropriate candidate and planned for primary transoral resection and/or neck dissection.
• ECOG performance status 0-1 at time of consent.
• Clinically or radiologically measurable disease; the primary tumor and/or neck nodes may be measurable according to RECIST 1.1(tumor diameter ≥ 1 cm; short-axis lymph node diameter ≥ 1.5 cm) OR by caliper measurement (tumor diameter ≥ 1 cm).
• Adequate hematologic, renal and hepatic function within 4 weeks of registration, as defined by:
• a) Absolute neutrophil count (ANC) ≥ 1,500/ul b) Creatinine ≤ 1.5 x institutional upper limit of normal (ULN). c) Bilirubin ≤ 1.5 x ULN, d) AST or ALT ≤ 2.5 x ULN. e) Fasting Serum amylase ≤ 2 × ULN f) Fasting Serum lipase ≤ ULN
• Note: A redraw is permitted within the 4 weeks for screening purposes.
• Ability to swallow and retain oral study medication as a whole tablet
• Have signed the written informed consent

You may not qualify if:

• Prior therapy for head and neck cancer is not allowed.
• Established diagnosis of diabetes mellitus type I or not controlled type II.
• Known hypersensitivity to alpelisib, or to any of the excipients of alpelisib.
• Currently documented pneumonitis (Note: The chest CT scan performed at baseline for the purpose of tumor assessment should be reviewed to confirm that there are no relevant pulmonary complications present).
• Any of the following cardiac abnormalities:
• Symptomatic congestive heart failure within 12 months prior to the start of study treatment
• History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy
• Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO).
• Myocardial infarction ≤ 6 months prior to start of study treatment
• Unstable angina pectoris
• Serious uncontrolled cardiac arrhythmia
• History of angina pectoris, coronary artery bypass graft (CABG), symptomatic pericarditis prior to the start of study treatment
• Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive medication. (Initiation or adjustment of antihypertensive medication(s) is allowed during screening; hypertension must be controlled prior to administering the study drug.) QTcF \> 480 msec on the screening ECG (using the QTcF formula)
• Currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
• Currently receiving any of the following medications and cannot be discontinued at least 7 days prior to the start of the treatment:

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

The University of Arizona Medical Center-University Campus

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Alpelisib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

This study stopped accrual early as the investigational product (IP) manufacturer, Novartis, terminated the study stopping provision of IP. 6 out of 20 subjects were accrued, 5 of which completed study. Due to early termination with few patients, only the counts of events have been calculated and no testing was done.

Results Point of Contact

• Title: Ricklie Julian, MD
• Organization: University of Arizona Cancer Center

rickliej@arizona.edu

520-694-2873

Study Officials

• Ricklie Julian, MD

  The University of Arizona Medical Center-University Campus

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: July 17, 2018
• First Posted: July 26, 2018
• Study Start: March 11, 2019
• Primary Completion: May 24, 2022
• Study Completion: May 24, 2022
• Last Updated: April 17, 2024
• Results First Posted: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)