Buparlisib + Chemotherapy for Head and Neck Cancer

(BURAN Trial)

Recruiting at 189 trial locations

Overseen By Namita Rao

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Adlai Nortye Biopharma Co., Ltd.

Must not be taking: CYP3A4 inhibitors, Torsades drugs

Disqualifiers: CNS metastases, Cardiac abnormalities, Depression, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: Up to 24 months

483 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for head and neck cancer that has returned or spread after standard treatments. Researchers aim to determine if adding buparlisib, a daily pill, to the common chemotherapy drug paclitaxel (also known as Taxol, Onxol, or Abraxane) improves outcomes compared to using paclitaxel alone. This trial targets individuals whose head and neck cancer has worsened despite previous treatments with specific immunotherapies and/or chemotherapy-based approaches. Participants should have undergone these therapies but not more than two rounds of systemic therapy for this type of cancer. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain drugs that affect liver enzymes (CYP3A4) or those that may cause heart rhythm issues. You may need to switch medications before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of buparlisib and paclitaxel has been studied previously. Results suggest this combination might help treat head and neck cancer when other treatments have failed. In earlier studies, some patients experienced side effects, typical for cancer treatments.

Previous studies also noted deaths during treatment in both the buparlisib and placebo groups, indicating some risks. However, the similar death rates in both groups suggest this treatment might be as safe as other available options.

Since this trial is in an advanced phase, the treatment has already been tested in people and is generally considered safe for more participants. Always discuss any concerns with a doctor, as they can provide advice specific to your situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Unlike the standard chemotherapy treatments for head and neck cancer, which generally involve drugs like cisplatin or carboplatin, the study treatment combines buparlisib with paclitaxel to offer a unique approach. Researchers are excited about buparlisib because it targets the PI3K pathway, which is often overactive in cancer cells, potentially leading to more effective cancer cell inhibition. This targeted mechanism differs from traditional treatments that broadly attack dividing cells, allowing for a more focused approach that could improve patient outcomes. The combination with paclitaxel, a drug already known for its efficacy, might enhance the overall effectiveness and provide new hope for patients with resistant or recurrent head and neck cancers.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that combining buparlisib and paclitaxel may help treat head and neck squamous cell carcinoma (HNSCC) that hasn't responded to other treatments. In this trial, one group of participants will receive this combination to evaluate its effectiveness for patients whose cancer has returned or spread after standard treatments like platinum-based chemotherapy. Evidence suggests that adding buparlisib to paclitaxel might lead to better results than using paclitaxel alone, which is being tested in a separate arm of this trial. This combination targets specific parts of cancer cells, potentially slowing their growth. Overall, researchers are carefully studying this combination for its potential to help patients with hard-to-treat HNSCC. ^{1 2 3 5 6}

Who Is on the Research Team?

Senior Director, Global Operations

Principal Investigator

Adlai Nortye USA Inc.

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have previously progressed after anti PD-1/PD-L1 therapy, alone or with platinum-based treatment. Participants must be in good physical condition, able to take oral medication, and not have had more than two systemic treatments for HNSCC.

Inclusion Criteria

Able to provide informed consent obtained before any trial related activities and according to local guidelines

I have had 2 or fewer treatments for head and neck cancer.

Patient has measurable disease as determined per RECIST version 1.1

Exclusion Criteria

Patient is pregnant or nursing

I have symptoms from cancer spread to my brain.

I have no cancer history, except for treated skin or in situ cancers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Buparlisib in combination with Paclitaxel or Paclitaxel alone. Treatment continues until disease progression, unacceptable toxicity, death, or discontinuation for any other reason.

Up to 24 months

Visits on Days 1, 8, and 15 of each 21-day cycle

Pharmacokinetics Sampling

Sparse PK sampling of Buparlisib on Treatment Cycle 1, Days 1, 8, and 15

15 days

PK sampling on Days 1, 8, and 15

Follow-up

Participants are monitored for safety and effectiveness after treatment. Anxiety and depression scores are assessed until 4 weeks following treatment discontinuation.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Buparlisib
• Paclitaxel

Trial Overview The BURAN study is testing the effectiveness of buparlisib combined with paclitaxel versus paclitaxel alone in patients whose HNSCC has worsened despite prior therapies. This phase III trial randomly assigns participants to either the combination treatment or the single drug.

How Is the Trial Designed?

Group I: Buparlisib & Weekly Paclitaxel Experimental Treatment 1 Intervention

Drug: Patients will receive 100 mg (2 x 50 mg) buparlisib hard gel capsule administered orally, once daily starting on Day 1 of Treatment Cycle 1, Drug: Paclitaxel (80 mg/m2) administered intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle. Treatment will continue until disease progression, unacceptable toxicity, death or discontinuation for any other reason.

Group II: Weekly Paclitaxel Active Control 1 Intervention

Patients will receive weekly paclitaxel (80 mg/m2) administered intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle. Treatment will continue until disease progression, unacceptable toxicity, death or discontinuation for any other reason.

Who Is Running the Clinical Trial?

Adlai Nortye Biopharma Co., Ltd.

Lead Sponsor

Trials

8

Recruited

740+

Published Research Related to This Trial

In a study of 46 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of weekly paclitaxel and cetuximab showed a promising overall response rate of 54%, with 22% achieving complete responses.

The treatment was well tolerated, with a disease control rate of 80% and median overall survival of 8.1 months, making it a potential option for patients who cannot receive platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Hitt, R., Irigoyen, A., Cortes-Funes, H., et al.[2022]

In a phase I trial involving 33 patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin demonstrated a 54% overall response rate, with 27% achieving complete responses, indicating significant efficacy in treating this patient population.

The maximum tolerated dose of paclitaxel was determined to be between 230 and 265 mg/m2, with manageable side effects, primarily grade 3/4 neutropenia and thrombocytopenia, suggesting that this treatment can be safely administered while potentially enhancing organ preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in head and neck cancer. Dunphy, F., Boyd, J., Dunleavy, T.[2015]

Paclitaxel shows promising activity against squamous cell carcinoma of the head and neck, with preliminary results from a phase II trial indicating two complete and seven partial responses among 19 patients.

While paclitaxel is effective, it is associated with significant toxicities, including grades 3 and 4 neutropenia and grades 1 and 2 neuropathy, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of paclitaxel (Taxol) in squamous cell carcinoma of the head and neck. Forastiere, AA.[2015]

In a phase 2 study involving 158 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of buparlisib (a pan-PI3K inhibitor) and paclitaxel significantly improved median progression-free survival to 4.6 months compared to 3.5 months with placebo plus paclitaxel, indicating enhanced clinical efficacy.

While the buparlisib group experienced a higher rate of grade 3-4 adverse events (82%) compared to the placebo group (72%), the safety profile was considered manageable, suggesting that buparlisib could be a viable second-line treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck (BERIL-1): a randomised, double-blind, placebo-controlled phase 2 trial. Soulières, D., Faivre, S., Mesía, R., et al.[2022]

In a phase II trial involving 30 patients with recurrent head and neck cancer, high-dose paclitaxel (250 mg/m2) demonstrated a 40% response rate, indicating its potential effectiveness as a treatment option.

The main side effects observed were neutropenia, peripheral neuropathy, and arthralgias/myalgias, which are consistent with previous studies, suggesting that while paclitaxel is promising, careful monitoring for these toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol) for the treatment of head and neck cancer. Forastiere, AA.[2015]

Weekly paclitaxel treatment in 74 patients with recurrent or metastatic head and neck cancer showed a 29% overall response rate, indicating promising efficacy in this challenging condition.

The treatment was associated with manageable side effects, with the most common severe adverse events being leukopenia and neutropenia, suggesting that while effective, careful monitoring of blood counts is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer. Tahara, M., Minami, H., Hasegawa, Y., et al.[2015]

In a pilot study involving 12 patients with recurrent and metastatic head and neck squamous cell carcinoma, the maximum tolerated dose of the PI3K inhibitor buparlisib was determined to be 100 mg daily when combined with cetuximab, and this combination was well-tolerated with no dose-limiting toxicities observed.

The combination treatment showed promising results, with one patient achieving a partial response and four others maintaining stable disease, indicating potential benefits for patients who had previously been treated with cetuximab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of the pan-class I PI3K inhibitor buparlisib in combination with cetuximab in patients with recurrent or metastatic head and neck cancer. Brisson, RJ., Kochanny, S., Arshad, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39808408/

Buparlisib and Paclitaxel in Patients with Head and Neck ... Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS6090

The BURAN study of buparlisib (AN2025) in combination ... Results suggest that buparlisib in combination with paclitaxel could be effective treatment following failure of platinum-based chemotherapy.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28131786/

a randomised, double-blind, placebo-controlled phase 2 trial Buparlisib in combination with paclitaxel could be an effective second-line treatment for patients with platinum-pretreated recurrent or metastatic squamous ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04338399

The BURAN Study of Buparlisib in Patients With Recurrent ... This study is to assess the impact on overall survival of the combination of Buparlisib and paclitaxel compared to paclitaxel alone in patients with prior anti ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01852292

NCT01852292 | Study of Efficacy and Safety of Buparlisib ... Phase II Study of efficacy and safety of buparlisib (BKM120) plus paclitaxel versus placebo plus paclitaxel in recurrent or metastatic Head and Neck cancer ...

6. ir.adlainortye.com ir.adlainortye.com/news-releases/news-release-details/adlai-nortye-announces-topline-results-phase-iii-buran-trial

Adlai Nortye Announces Topline Results of Phase III BURAN ... This Phase III trial builds on positive Phase II data, where the buparlisib-paclitaxel combination demonstrated improvements in ORR, PFS, and OS ...