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NCT03601507

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

Terminated Phase 2 Results posted Last updated 17 April 2024
What this trial tests

Phase 2 trial testing Alpelisib in CDKN2A-p16 Positive in 9 participants. Terminated before completion.

Timeline
11 March 2019
Primary endpoint
24 May 2022
24 May 2022

Quick facts

Lead sponsorUniversity of Arizona
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment9
Start date11 March 2019
Primary completion24 May 2022
Estimated completion24 May 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Arizona

Who can join

Eligibility, any sex, with CDKN2A-p16 Positive or HPV Positive Oropharyngeal Squamous Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Stable disease
GroupValue95% CI
Treatment (Alpelisib)4
Partial response
GroupValue95% CI
Treatment (Alpelisib)1
Complete response
GroupValue95% CI
Treatment (Alpelisib)0
Progressive disease
GroupValue95% CI
Treatment (Alpelisib)0
Non-evaluable
GroupValue95% CI
Treatment (Alpelisib)1
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) Primary · Baseline up to 28 days

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.

GroupValue95% CI
Treatment (Alpelisib)7.60 – 33.4
Percentage of Participants With Adverse Events Secondary · 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.

Diarrhea
GroupValue95% CI
Treatment (Alpelisib)3
Creatinine Increased
GroupValue95% CI
Treatment (Alpelisib)1
Acute Kidney Injury
GroupValue95% CI
Treatment (Alpelisib)1
Maculopapular rash
GroupValue95% CI
Treatment (Alpelisib)2
Hyperglycemia
GroupValue95% CI
Treatment (Alpelisib)2
Surgical Complications Secondary · 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.

GroupValue95% CI
Treatment (Alpelisib)5
Treatment (Alpelisib)0
Length of Hospital Stay Secondary · 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.

GroupValue95% CI
Treatment (Alpelisib)5.83 – 9

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Alpelisib)
Serious: 0/6 (0%)
Deaths: 0/6
Other adverse events (4 terms — click to expand)

ReactionSystemTreatment (Alpelisib)
DiarrheaGastrointestinal disorders
Maculopapular rashSkin and subcutaneous tissue disorders
HyperglycemiaMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders

Data from ClinicalTrials.gov NCT03601507 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
    Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
  2. The emerging role of PI3K inhibitors for solid tumour treatment and beyond.
    Belli C, Repetto M, Anand S, Porta C, et al · · 2023 · cited 53× · PMID 36914722 · DOI 10.1038/s41416-023-02221-1
  3. Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.
    Ghosh S, Shah PA, Johnson FM. · · 2022 · cited 47× · PMID 35887235 · DOI 10.3390/ijms23147889
  4. Therapeutic implications of activating noncanonical PIK3CA mutations in head and neck squamous cell carcinoma.
    Jin N, Keam B, Cho J, Lee MJ, et al · · 2021 · cited 47× · PMID 34779417 · DOI 10.1172/jci150335
  5. De-Escalating Strategies in HPV-Associated Head and Neck Squamous Cell Carcinoma.
    Economopoulou P, Kotsantis I, Psyrri A. · · 2021 · cited 15× · PMID 34578368 · DOI 10.3390/v13091787
  6. Molecular pathways and targeted therapies in head and neck cancers pathogenesis.
    Constantin M, Chifiriuc MC, Bleotu C, Vrancianu CO, et al · · 2024 · cited 9× · PMID 38952548 · DOI 10.3389/fonc.2024.1373821
  7. New insights into RAS in head and neck cancer.
    Jagadeeshan S, Novoplansky OZ, Cohen O, Kurth I, et al · · 2023 · cited 8× · PMID 37619805 · DOI 10.1016/j.bbcan.2023.188963
  8. Targeted Therapy as a Potential De-Escalation Strategy in Locally Advanced HPV-Associated Oropharyngeal Cancer: A Literature Review.
    Chitsike L, Duerksen-Hughes PJ. · · 2021 · cited 6× · PMID 34490123 · DOI 10.3389/fonc.2021.730412

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