Trial Outcomes & Findings for Alpelisib in Treating Participants With Transorally Resectable HPV-Associated Stage I-IVA Oropharyngeal Cancer (NCT NCT03601507)

NCT ID: NCT03601507

Last Updated: 2024-04-17

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

Baseline up to 28 days

Results posted on

2024-04-17

Participant Flow

9 out of 14 patients were accrued to the trial from March 2019 to Feb 2023. The study closed to accrual prematurely in February 2023 as the drug manufacturer, Novartis pulled support for the study. 3 patients were ineligible, 6 patients started the study.

Participant milestones

Participant milestones
Measure	Treatment (Alpelisib) 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
Overall Study STARTED	6
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Alpelisib) 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
Overall Study Adverse Event	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Alpelisib) n=6 Participants 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
Age, Continuous	60.69 years STANDARD_DEVIATION 7.70 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 days

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.

Outcome measures

Outcome measures
Measure	Treatment (Alpelisib) n=6 Participants 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
Quantitative Change in the Sum of Response Evaluation Criteria in Solid Tumors (RECIST) - Stable disease	4 Participants
Quantitative Change in the Sum of Response Evaluation Criteria in Solid Tumors (RECIST) - Partial response	1 Participants
Quantitative Change in the Sum of Response Evaluation Criteria in Solid Tumors (RECIST) - Complete response	0 Participants
Quantitative Change in the Sum of Response Evaluation Criteria in Solid Tumors (RECIST) - Progressive disease	0 Participants
Quantitative Change in the Sum of Response Evaluation Criteria in Solid Tumors (RECIST) - Non-evaluable	1 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 days

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

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.

Outcome measures

Outcome measures
Measure	Treatment (Alpelisib) n=5 Participants 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
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)	7.6 percent change Interval 0.0 to 33.4

SECONDARY outcome

Timeframe: Baseline up to 28 days

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

Outcome measures

Outcome measures
Measure	Treatment (Alpelisib) n=6 Participants 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
Percentage of Participants With Adverse Events Diarrhea	3 Participants
Percentage of Participants With Adverse Events Creatinine Increased	1 Participants
Percentage of Participants With Adverse Events Acute Kidney Injury	1 Participants
Percentage of Participants With Adverse Events Maculopapular rash	2 Participants
Percentage of Participants With Adverse Events Hyperglycemia	2 Participants

SECONDARY outcome

Timeframe: Baseline up to 28 days

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.

Outcome measures

Outcome measures
Measure	Treatment (Alpelisib) n=5 Participants 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
Surgical Complications No surgical complications	5 Participants
Surgical Complications Surgical complications	0 Participants

SECONDARY outcome

Timeframe: Baseline up to 28 days

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.

Outcome measures

Outcome measures
Measure	Treatment (Alpelisib) n=5 Participants 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
Length of Hospital Stay	5.8 days Interval 3.0 to 9.0

SECONDARY outcome

Timeframe: Baseline up to 28 days

Population: Data was not collected for this outcome measure.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 28 days

Population: data was not collected for this outcome measure

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 28 days

Population: data was not collected for this outcome measure

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 28 days

Population: Data was not collected for this outcome measure

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

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Alpelisib)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment (Alpelisib) n=6 participants at risk 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
Gastrointestinal disorders Diarrhea	50.0% 3/6 • Number of events 3 • Adverse events were collected from each patient from the time of their first treatment with study drug. Subjects received study drug for 10-21 days. At the 4-week follow up visit, adverse drug reactions were followed until return to baseline or stabilization. At the 4 week follow-up visit, only adverse drug reactions were documented. 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
Renal and urinary disorders Acute kidney injury	16.7% 1/6 • Number of events 1 • Adverse events were collected from each patient from the time of their first treatment with study drug. Subjects received study drug for 10-21 days. At the 4-week follow up visit, adverse drug reactions were followed until return to baseline or stabilization. At the 4 week follow-up visit, only adverse drug reactions were documented. 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
Skin and subcutaneous tissue disorders Maculopapular rash	33.3% 2/6 • Number of events 4 • Adverse events were collected from each patient from the time of their first treatment with study drug. Subjects received study drug for 10-21 days. At the 4-week follow up visit, adverse drug reactions were followed until return to baseline or stabilization. At the 4 week follow-up visit, only adverse drug reactions were documented. 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
Metabolism and nutrition disorders Hyperglycemia	33.3% 2/6 • Number of events 3 • Adverse events were collected from each patient from the time of their first treatment with study drug. Subjects received study drug for 10-21 days. At the 4-week follow up visit, adverse drug reactions were followed until return to baseline or stabilization. At the 4 week follow-up visit, only adverse drug reactions were documented. 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

Additional Information

Ricklie Julian, MD

University of Arizona Cancer Center

Phone: 520-694-2873

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place