Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

All Drugs and Chemicals

Phosphoinositide-3 Kinase Inhibitors

Enzyme Inhibitors

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.

Alpelisib

Laboratory Biomarker Analysis

Pharmacodynamic Study

Therapeutic Conventional Surgery

Ricklie Julian, MD

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.

PRIMARY OBJECTIVES:

I. To assess the preliminary efficacy of neoadjuvant Alpelisib (BYL719) in patients with transorally-resectable, HPV+ head and neck squamous cell carcinoma (HNSCC), as measured by quantitative change in tumor size (change in T) following 14-21 days of treatment.

II. To evaluate the relationship between genomic PIK3CA activation to change in T.

SECONDARY OBJECTIVES:

I. To describe the tolerability of brief neoadjuvant exposure to BYL719. II. To assess the effect of BYL719 on the tumoral Ki-67 proliferation index. III. To evaluate viral and molecular mediators of response and resistance to BYL719, including viral messenger ribonucleic acid (mRNA), E6 and E7 oncoproteins, and phosphorylated (p)HER3.

OUTLINE:

Participants receive Alpelisib orally (PO) once daily (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.

After completion of study treatment, participants are followed up for up to 12 weeks.

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

Biomarker Modulation by Alpelisib (BYL719) in Transorally Resectable, HPV-Associated HNSCC: A Phase II Window Trial

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.

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.

Will be reported descriptively, including tabulation of toxicities according to National Cancer Institut (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.

The safety of this window intervention will be reported descriptively, including tabulation of toxicities according to NCI CTCAE v.4.03, surgical complications, and length of hospital stay.

We hypothesize that BYL719 will reduce HPV mRNA, and this will correlate with decrease in tumor size.

We hypothesize that BYL719 will decrease tumoral E6 and E7 oncoprotein levels, and this will correlate with decrease in tumor size

We hypothesize that pHER3 is a resistance mechanism for BYL719, and that pHER3 will be upregulated in non-responders.

We hypothesize that HER3/PI3K dimerization is a resistance mechanism for BYL719, and that dimers will be upregulated in non-responders.

National Cancer Institute (NCI)

University of Arizona

Only AEs meeting one of the following criteria were collected.

* Any AE that is Grade 3 or higher, regardless of relationship to the study drug
* Any intolerable Grade 2 AE
* Any Grade AE resulting in holding or dose-reducing BYL719
* Any Grade 2 laboratory or vital sign values that are deemed clinically significant by the treating investigator
* Any Grade AE in the following categories of interest:

  * Rash
  * Diarrhea
  * Pneumonitis
  * Hyperglycemia

Participants receive Alpelisib PO QD for 10-21 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.

Alpelisib: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pharmacodynamic Study: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Treatment (Alpelisib)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

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.

Stable disease

Partial response

Complete response

Progressive disease

Non-evaluable

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

Change in tumor size is presented here. Correlative analysis for this outcome will be completed in the upcoming months.

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)

Diarrhea

Creatinine Increased

Acute Kidney Injury

Maculopapular rash

Hyperglycemia

Percentage of Participants With Adverse Events

Surgical Complications

Length of Hospital Stay

Data was not collected for this outcome measure.

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

data was not collected for this outcome measure

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

Changes in Pre- and Post-treatment Tumor Levels of Phospho - Human Epidermal Growth Factor Receptor 3 (HER3)

Data was not collected for this outcome measure

Spots Global Cancer Trial Database for stage ii oropharyngeal squamous cell carcinoma ajcc v7