BYL719 for Head and Neck Cancer

Overseen By Eric Winquist

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must not be taking: CYP34A/CYP2C8 inhibitors, QT prolonging drugs

Disqualifiers: Metastatic disease, Diabetes, GI disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called BYL719, a targeted cancer therapy, to determine its effectiveness in treating head and neck cancer before surgery. Researchers aim to assess the drug's impact by examining changes in the tumor's genes. Individuals with head and neck cancer scheduled for surgical treatment and who can swallow pills may qualify for this study. The study seeks to understand the drug's effect on cancer cells and its potential role in treatment. As an unphased trial, it offers patients the chance to contribute to groundbreaking research that could enhance future cancer treatments.

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications, such as those that affect specific liver enzymes (CYP34A or CYP2C8), medications that prolong the QT interval, and warfarin. You must discontinue these at least 1 week before starting the study treatment, but switching to a different medication is allowed.

Is there any evidence suggesting that BYL719 is likely to be safe for humans?

Research has shown that BYL719, also known as Alpelisib, has been studied for its safety in humans. In one study, researchers combined BYL719 with cetuximab to treat head and neck cancers. Some patients experienced side effects such as mouth sores, high blood sugar, and infections at the feeding tube site, mostly linked to higher doses.

Another study found that the highest dose tested sometimes caused serious side effects, preventing further dose increases. However, most patients tolerated a lower dose well, experiencing no major problems.

Overall, BYL719 has shown some side effects, but many patients tolerated it, especially at lower doses. This suggests it might be safe for further testing in humans, with careful monitoring of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for head and neck cancer, which often include surgery, radiation, and chemotherapy, BYL719 is a targeted therapy that specifically inhibits the PI3K pathway, a key driver in many cancers. This pathway is often overactive in cancer cells, leading to their growth and survival. By targeting this mechanism, BYL719 offers a more precise approach that could potentially reduce side effects compared to conventional treatments. Researchers are excited about BYL719 because it represents a new way to attack cancer cells directly, potentially leading to more effective and less toxic treatment options.

What evidence suggests that BYL719 might be an effective treatment for head and neck cancer?

Research has shown that BYL719, also known as alpelisib, yields promising results in treating head and neck squamous cell carcinoma (HNSCC). Studies found that combining BYL719 with cetuximab effectively fights tumors in this cancer type. Patients generally tolerate this combination well, leading to positive outcomes and suggesting its potential effectiveness. BYL719 targets the PI3K pathway, which often contributes to cancer growth, and works well when PI3K is significant in the cancer cells. This makes BYL719 a hopeful option for treating HNSCC, especially when traditional treatments might not be as effective. ^{1 2 3 4 6}

Who Is on the Research Team?

Anthony Nichols

Principal Investigator

London Health Sciences Centre

Are You a Good Fit for This Trial?

Adults with resectable head and neck squamous cell carcinoma (HNSCC) who can undergo surgery, have a life expectancy over 6 months, and proper organ function. They must not be pregnant, agree to use contraception, and should not have had certain treatments or conditions that could affect the study drug's intake or efficacy.

Inclusion Criteria

My doctor has checked my medications and made necessary adjustments.

My cancer is a type of squamous cell carcinoma located in the head or neck.

Life expectancy of greater than 6 months

Exclusion Criteria

Patient has history of hypersensitivity to any drugs or metabolites or similar chemical classes as BYL719

I am on medication that affects my heart's rhythm and cannot change it.

Patients with known positive serology for human immunodeficiency virus (HIV)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BYL719 orally daily at the maximum tolerated dose (400 mg/day) for 14 days

2 weeks

Daily oral administration

Surgery

All patients will receive surgery as the standard of care

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BYL719

Trial Overview The trial is testing BYL719 in patients with HNSCC before they go for surgery. It aims to see how this drug affects cancer biomarkers. Participants will take BYL719 orally in a single-center study designed to prepare them for their upcoming surgical treatment.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 1 Intervention

14 days of BYL719 treatment, open label

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9478566/

A Phase Ib Study of Cetuximab and BYL719 (Alpelisib) ... This is a single-institution phase I study that evaluated the addition of BYL719, an α-specific PI3K inhibitor, to cetuximab and intensity-modulated radiation ...

2. e-crt.org e-crt.org/journal/view.php?number=3725

Differential Efficacy of Alpelisib by PIK3CA Mutation Site in ... Unfortunately, patients with R/M HNSCC experience poor survival outcomes, with a median overall survival (OS) of approximately 1 year.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10663259/

A Phase 1b/2 Study of Alpelisib in Combination with ... Alpelisib in combination with cetuximab showed synergistic anti-tumour activity in head and neck squamous cell carcinoma (HNSCC) models.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01602315

A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent ... This was a multi-center, open-label, Phase Ib dose escalation /Phase II study in recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) ...

5. ascopubs.org ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.6044

Phase lb/ll study of the PI3Kα inhibitor BYL719 in ... Combined inhibition of PI3K-a and EGFR by BYL719 and cetuximab was tolerated and demonstrated encouraging antitumor activity.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S036030161933963X

A Phase 1b Study of Cetuximab and BYL719 (Alpelisib) ... Eleven patients were evaluable. Dose level 2 was the maximum tolerated dose for BYL719. Two patients on dose level 3 had dose-limiting toxicities of oral ...