The BURAN Study of Buparlisib (AN2025) In Combination with Paclitaxel Compared to Paclitaxel Alone in patients with head and neck cancer

Phase 1

• Conditions: Head and Neck Squamous Cell Carcinoma (HNSCC); MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000790-23-PL
• Lead Sponsor: Adlai Nortye USA Inc.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-24
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 483

Inclusion Criteria

Patients must meet the following criteria to be eligible for enrollment into the study:
1. Aged =18 years old.
2. Able to provide informed consent obtained before any study related activities and according to local guidelines.
3. Patient has histologically and/or cytologically-confirmed HNSCC.
4. Patient has archival or new tumor tissue for the analysis of biomarkers and confirmation of HPV status (if unknown). A recommended minimum of 5 slides for patients with known HPV status (for tumor DNA characterization) or a recommended minimum of 10 slides for patients whose HPV status is unknown (i.e. 5 slides for HPV testing and 5 slides for biomarker testing). Enrollment in the study is contingent on confirmation of the availability of an adequate amount of tumor tissue, except in rare special circumstances, which must be reviewed and approved by the sponsor. The quantity of slides to be provided is a recommendation; more slides may be requested to ensure testing can be complete.
5.Patient has either progressive or recurrent disease after treatment with PDL1/PD1 based therapy for recurrent or metastatic disease:
a.PDL1/PD1 therapy alone for metastatic or recurrent (monotherapy) disease
b.PDL1/PD1 in combination with chemotherapy for metastatic or recurrent disease
c.PDL1/PD1 used for metastatic disease, after or prior to receiving a platinum agent for locally advanced or metastatic disease.
d. For France patients only a specific inclusion criteria was added - please refer to PA5.01.
6.Patient has received no more than two prior lines of systemic treatment for recurrent or metastatic HNSCC (single agent chemotherapy used as a radiosensitizer is not counted as a prior line of therapy).
7. Patient has measurable disease as determined per RECIST version 1.1. If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a four-week period since radiotherapy completion is required.
8. Patient has adequate bone marrow function and organ function as shown by the following:
a. Absolute neutrophil count (ANC) = 1.5 x 109/L.
b. Hemoglobin = 9 g/dL (which may be reached by transfusion).
c. Platelets = 100 x 109/L (which may be reached by transfusion).
d. International normalized ratio (INR) = 1.5.
e. Calcium (corrected for serum albumin) within normal limits (WNL) or = grade 1 severity according to NCI-CTCAE version 5.0 if judged clinically not significant by the Investigator. Patients concomitantly taking bisphosphonates or denosumab for calcium correction are eligible.
f. Normal potassium and magnesium levels or clinically acceptable levels as per investigator’s judgement and confirmation
For France patients only a specific inclusion criteria was added - please refer to PA5.01.
g. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) = 1.5 x upper limit of normal (ULN) or < 3.0 x ULN if liver metastases are present.
h. Total serum bilirubin = ULN or = 1.5 x ULN if liver metastases are present; or total bilirubin = 3.0 x ULN with direct bilirubin below or within normal range in patients with well documented Gilbert’s Syndrome. Gilbert’s syndrome is defined as presence of episodes of unconjugated hyperbilirubinemia with normal results from cells blood count (including normal reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease processes at the time of diagnosis.
i. Serum creatinine = 1.5 x ULN or calculated and directly m

Exclusion Criteria

1. Patient has received previous treatment with any protein kinase B
(PKB/AKT), mammalian target of rapamycin (mTOR) inhibitors, or phosphatidylinositol 3 kinase (PI3K) pathway inhibitors. 2. Patient received treatment with a taxane as part of prior treatment for recurrent or metastatic disease. 3. Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this study. Patient must have completed any prior local treatment for CNS metastases = 28 days prior to the start of study treatment (including radiotherapy) and must be on a stable low dose of corticosteroid therapy. Radiosurgery must have been completed at least 14 days prior to start of study treatment. 4. Patient has received wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting study treatment or who have adverse events which have not recovered to grade 1 or better from previous chemotherapy treatment (except alopecia, autoimmune endocrine events must be stable and controlled). 5. Patient has grade = 2 neuropathy, colitis, pneumonitis, and uncontrolled endocrinopathies (e.g., hypothyroidism, diabetes with hemoglobin A1c > 8%) from previous treatment. 6. Patient has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects. 7. Patient is currently receiving increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent. The following uses of corticosteroids are permitted: single doses; standard premedication for paclitaxel, topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops, or local injections (e.g., intra-articular), or < 10 mg prednisolone or equivalent. 8. Patient is being treated at start of study treatment with any of the following drugs: a. Drugs known to be strong or moderate inhibitors or inducers of isoenzyme cytochrome P450 3A4 (CYP3A4) including herbal medications. b. Drugs with a known risk of inducing Torsades de Pointes. 9. Patient is currently receiving warfarin or other coumarin-derived anti-coagulant, for treatment, prophylaxis, or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), fondaparinux or new oral anticoagulants (NOACs) is allowed. 10. Patient has a known hypersensitivity and/or contraindication to paclitaxel, standard premedication for paclitaxel, or other products containing Cremophor®.11.Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the Investigator's judgment, contraindicate patient participation in the clinical study.
12. Patient has a known history of HIV infection (testing not mandatory). 13. Patient has any of the following cardiac abnormalities:a.Symptomatic congestive heart failure within 12 months of the screening period, History of documented congestive heart failure or documented cardiomyopathy and left ventricular ejection fraction (LVEF) <50% as determined by multiple gated acquisition (MUGA) scan or ECHO, Myocardial infarction =six months prior to enrollment, Unstable angina pectoris, Serious uncontrolled cardiac arrhythmia, Symptomatic pericarditis, QT interval corrected according to the formula of Fridericia (QTcF) > 450 msec for males and > 470 msec for females, on the screening ECG, Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified