AzTrials
AzTrials

CDKN2A-p16 PositivePhase 2NCT03601507

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

A Phase 2 study testing Alpelisib, Laboratory Biomarker Analysis and Pharmacodynamic Study in people with CDKN2A-p16 Positive and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by University of Arizona at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
Alpelisib, Laboratory Biomarker Analysis and Pharmacodynamic Study
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
11 Mar 2019to 24 May 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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:
  • 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

Who cannot join

  • 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
Show all 40Show fewer
  • 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:
  • Medications that have a known risk to prolong the QT interval or induce Torsade de Pointes (TdP) and the treatment cannot be discontinued or switched to a different medication prior to starting treatment with BYL719 (refer to list of prohibited QT prolonging drugs provided in in Appendix 3)
  • Herbal preparations/medications
  • Currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week prior to the start of study treatment and must have discontinued strong inhibitors before the start of treatment. Switching to a different medication prior to randomization is allowed; (Refer to Appendix 2 and 3, Tables 1 and 2) for permitted and non-permitted medications).
  • History of acute pancreatitis within1 year of screening or past medical history of chronic pancreatitis
  • Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • History of Stevens-Johnson-Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).
  • Known positive serology for human immunodeficiency virus (HIV)
  • Any other condition, including severe and/or uncontrolled medical conditions, that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, unable to swallow oral study medication as a whole tablet, social/psychological complications
  • Currently taking herbal preparations/medications and dietary supplements (except for vitamins) and unwilling to stop.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)
  • Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment:
  • Sexually active males must use a condom during intercourse while taking BYL719 and for 1 week after the final dose of BYL719, and should not father a child in this period, but may be recommended to seek advice on conservation of sperm. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least 1 week after the final dose of BYL719. Highly effective contraception is defined as either:
  • Total abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception].
  • Female sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment iii. Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). [For female study subjects, the vasectomized male partner should be the sole partner for that patient] iv. Use a combination of the following (both 1+2):
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
  • Note: Hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed as BYL719 may decrease the effectiveness of hormonal contraceptives.
  • NOTE: Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago.
  • 17. Active systemic infection requiring systemic antibiotics or anti-fungals within 7 days prior to first dose of study drug.
  • Note: Active topical infections (for example oral thrush) do not exclude a subject even if treated with systemic antibiotics or systemic antifungals.
  • 18. Chronic hepatitis
  • 19. Severely impaired lung function
  • 20. Unresolved osteonecrosis of the jaw
  • 21. Prisoners or individuals who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The University of Arizona Medical Center-University Campus

    Tucson, Arizona, 85724

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Alpelisib, Laboratory Biomarker Analysis, Pharmacodynamic Study, Therapeutic Conventional Surgery
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlpelisibDrug

    Also called BYL719, Phosphoinositide 3-kinase Inhibitor BYL719

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacodynamic StudyOther

    Also called PHARMACODYNAMIC

    Correlative studies

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo surgery

Study groups in NCT03601507
Study groupRoleWhat they receive
Treatment (Alpelisib)ExperimentalParticipants 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.
Receives: Drug: Alpelisib; Other: Laboratory Biomarker Analysis; Other: Pharmacodynamic Study; Procedure: Therapeutic Conventional Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline up to 28 days

  2. 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.

    Measured: Baseline up to 28 days

Secondary outcomes (7)

  1. Percentage of Participants With Adverse Events

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

    Measured: Baseline up to 28 days

  2. Surgical Complications

    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.

    Measured: Baseline up to 28 days

  3. Length of Hospital Stay

    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.

    Measured: Baseline up to 28 days

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

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

    Measured: Baseline up to 28 days

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

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

    Measured: Baseline up to 28 days

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

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

    Measured: Baseline up to 28 days

  7. Changes in Pre- and Post-treatment Tumor Levels of HER3/PI3K Dimers (Monogram)

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

    Measured: Baseline up to 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2018
  2. Study start11 Mar 2019
  3. Primary completion24 May 2022
  4. Study completion24 May 2022

Why it stopped: Novartis has chosen to withdraw support for this trial

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03601507
Sponsor's protocol ID
1802258478
Other IDs
NCI-2018-00507, CBYL719XUS15T, 1802258478, P30CA023074
Status last verified
Apr 2024
First submitted
17 Jul 2018
Last updated
17 Apr 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpelisib, Laboratory Biomarker Analysis and Pharmacodynamic Study in people with CDKN2A-p16 Positive and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by University of Arizona at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Quantitative Change in the Sum of Response Evaluation Criteria in Solid Tumors (RECIST) - (time frame: Baseline up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03601507.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in