What side effects are associated with this type of intervention?

Common treatments for head and neck cancers, such as chemotherapy (cisplatin, paclitaxel), targeted therapies (cetuximab), and immunotherapies (pembrolizumab), have various side effects. Chemotherapy often causes nausea, fatigue, decreased appetite, and hematologic toxicities. Targeted therapies like cetuximab can lead to skin reactions, hypomagnesemia, and infusion-related reactions. Immunotherapies such as pembrolizumab may result in immune-related adverse events, including colitis, pneumonitis, and thyroid dysfunction. Buparlisib, a PI3K inhibitor, has been associated with fatigue, nausea, decreased appetite, and hypoalbuminemia.

What prior FDA approvals exist?

The FDA has approved several treatments for head and neck cancers, including cetuximab, a monoclonal antibody targeting the EGFR pathway, and pembrolizumab, an immune checkpoint inhibitor targeting PD-1. While Buparlisib, a PI3K inhibitor, is still under investigation, other drugs targeting similar pathways, such as farnesyltransferase inhibitors for HRAS mutant squamous cell carcinoma, have shown promise in clinical trials. These treatments highlight the ongoing efforts to target specific molecular pathways in head and neck cancers.

What other types of research exist?

Promising novel alternatives to Buparlisib for head and neck cancer patients include: 1) Farnesyltransferase inhibitors like tipifarnib, which have shown objective response rates of up to 56% in HRAS mutant squamous cell carcinoma. 2) Pembrolizumab plus cetuximab, which demonstrated overall responses in 45% of patients in a phase II trial. 3) Metronomic chemotherapy combined with low-dose nivolumab, which improved overall survival in a phase III trial. 4) Small molecule tyrosine kinase inhibitors such as afatinib and gefitinib, although their clinical roles are still being established.

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PI3K Inhibitor

Buparlisib + Chemotherapy for Head and Neck Cancer (BURAN Trial)

Phase 3

Waitlist Available

Research Sponsored by Adlai Nortye Biopharma Co., Ltd.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient has received no more than two prior lines of systemic treatment for HNSCC

Aged ≥18 years old

Must not have

Patient has symptomatic central nervous system (CNS) metastases

Patient has any of the following cardiac abnormalities

Timeline

Screening 3 weeks

Treatment Varies

Follow Up orr will be assessed for all patients 6 months after randomization is complete.

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Buparlisib may cause high blood sugar levels, rash, fatigue, nausea and liver issues. Paclitaxel can lead to allergic reactions, low blood cell counts increasing infection risk, nerve damage causing numbness or pain and muscle aches.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 18 years old or older.

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I can swallow and keep down pills.

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My cancer diagnosis was confirmed through tissue examination.

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My cancer returned or worsened after treatment with PD1/PDL1 therapy.

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I am fully active and can carry on all pre-disease activities without restriction.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have symptoms from cancer spread to my brain.

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I have a heart condition.

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I have a stomach or intestine problem that affects how I absorb medicine.

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I have a history of or currently have a major mental health condition.

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I am currently taking medication that strongly affects liver enzyme CYP3A4.

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I am allergic to paclitaxel or its common premedications.

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I had major surgery less than 2 weeks ago.

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I have used a cancer treatment drug within the last 4 weeks.

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I have severe nerve pain, inflammation of the colon or lungs, or hormone imbalances from past treatments.

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I am currently taking warfarin or a similar blood thinner.

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I am on long-term steroids or other drugs that weaken my immune system.

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I have been treated with a taxane for my metastatic disease.

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I have been treated with drugs targeting the PKB/AKT, mTOR, or PI3K pathways.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ orr will be assessed for all patients 6 months after randomization is complete.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~orr will be assessed for all patients 6 months after randomization is complete.

This trial's timeline: 3 weeks for screening, Varies for treatment, and orr will be assessed for all patients 6 months after randomization is complete. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival (OS)

Secondary study objectives

Health Related Quality of Life (QoL): Time to Definitive deterioration of Quality of Life as assessed by EORTC C30 questionnaire

Overall Response Rate

Pharmacokinetics of Buparlisib: plasma concentration-time profile of Buparlisib during 15 days of treatment

+2 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Buparlisib & Weekly PaclitaxelExperimental Treatment1 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 PaclitaxelActive Control1 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.

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Head and Neck Cancers (HNSCC) often involve alterations in the PI3K/AKT/mTOR signaling pathway, which regulates cell growth, metabolism, and survival. PI3K inhibitors, such as Buparlisib, target this pathway to reduce tumor growth and proliferation. Additionally, EGFR inhibitors like cetuximab block the epidermal growth factor receptor, which is often overexpressed in HNSCC, thereby inhibiting cell division and promoting apoptosis. Immunotherapy, particularly PD-L1 checkpoint inhibitors, enhances the immune system's ability to recognize and destroy cancer cells. These targeted treatments are crucial for HNSCC patients as they offer more personalized and potentially effective options compared to traditional chemotherapy, addressing specific molecular abnormalities within the tumors.

An evaluation of buparlisib for the treatment of head and neck squamous cell carcinoma.A controlled trial of HNSCC patient-derived xenografts reveals broad efficacy of PI3Kα inhibition in controlling tumor growth.Combination of phosphotidylinositol-3-kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer.