Buparlisib + Chemotherapy for Head and Neck Cancer

(BURAN Trial)

Recruiting at 162 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

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, buparlisib and paclitaxel, for patients with head and neck cancer that has returned or spread after other treatments. Buparlisib is taken regularly to stop cancer cells from growing, and paclitaxel is given periodically to prevent them from multiplying. The goal is to see if this combination works better than using paclitaxel alone.

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.

What data supports the effectiveness of the drug combination Buparlisib and Paclitaxel for head and neck cancer?

Research shows that adding Buparlisib to Paclitaxel can improve outcomes for patients with recurrent or metastatic head and neck cancer, as Buparlisib targets a pathway that often leads to treatment resistance. Additionally, Paclitaxel has been effective in treating similar conditions, providing further support for this combination. ^{1 2 3 4 5}

Is the combination of Buparlisib and Paclitaxel safe for treating head and neck cancer?

Buparlisib has been studied with cetuximab for head and neck cancer, and paclitaxel has been tested in various combinations for the same condition. Common side effects of paclitaxel include neutropenia (low white blood cell count) and neuropathy (nerve damage), while buparlisib's safety profile is still being evaluated. ^{4 5 6 7 8}

What makes the drug combination of Buparlisib and Paclitaxel unique for head and neck cancer?

The combination of Buparlisib, a pan-PI3K inhibitor, and Paclitaxel is unique because it targets the PI3K pathway, which is often activated in head and neck cancer and contributes to treatment resistance. This combination has shown improved outcomes in patients with specific genetic profiles, such as those with TP53 alterations or HPV-negative status, compared to Paclitaxel alone. ^{3 4 5 9 10}

Research Team

Senior Director, Global Operations

Principal Investigator

Adlai Nortye USA Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel in patients with recurrent or metastatic head and neck cancer. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Phase I study of nab-paclitaxel-based induction followed by nab-paclitaxel-based concurrent chemotherapy and re-irradiation in previously treated head and neck squamous cell carcinoma. [2023]

3. England 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. [2022]

4. United States 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. [2022]

5. England 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in head and neck cancer. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

The role of paclitaxel in the treatment of head and neck cancer. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

Molecular Alterations and Buparlisib Efficacy in Patients with Squamous Cell Carcinoma of the Head and Neck: Biomarker Analysis from BERIL-1. [2019]