The BURAN Study of Buparlisib (AN2025) In Combination with Paclitaxel Compared to Paclitaxel Alone in patients with head and neck cancer
- Conditions
- Head and Neck Squamous Cell Carcinoma (HNSCC)MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000790-23-IT
- Lead Sponsor
- Adlai Nortye USA Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 489
Aged =18yo.
Able to provide ICFobtained before any study related activities.
PT has histologically and/or cytologically-confirmed HNSCC.
Patient has archival or new tumor tissue for the analysis of
biomarkers. A tumor block (preferred) or a minimum of 12 (15
recommended) unstained slides to be provided. Enrollment in the study
is contingent on confirmation of an adequate amount of tumor tissue.
Patients progressing following treatment with an anti PD 1/anti PD L1 therapy are encouraged to have a new tumor biopsy for biomarker analysis.
PT has either progressive or recurrent disease after treatment with PDL1/PD1 based therapy for recurrent or metastatic disease:
PDLl/PD1 therapy alone for metastatic (monotherapy) disease
PDL1/PD1 in combination with chemotherapy for metastatic and
recurrent disease PDL1/PD1 used for metastatic disease, after or prior to receiving a
platinum agent for locally advanced or metastatic disease.
PT has received no more than two prior lines of systemic
treatment for HNSCC (single agent chemotherapy used as a
radiosensitizer is not counted as a prior line of therapy).
PT 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.
PT has adequate bone marrow function and organ function as
shown by the following:
ANC=1.5x109/L.
Hemoglobin=9g/dL (which may be reached by transfusion).
Platelets=100x109/L (which may be reached by transfusion).
International normalized ratio (INR) = 1.5.
Ca(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.
AST and ALT=1.5 xULNor<3.0xULN if liver metastases
are present.
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.
Serum creatinine = 1.5 x ULN or calculated or directly measured
creatinine clearance (CrCL) > 30 mL/min.
I. Haemoglobin A1c (glycosylated hemoglobin; HbA1c) =8%.
Patient has Eastern Cooperative Oncology Group (ECOG) performance
status =1.
Patient is able to swallow and retain oral medication. Patients able to
swallow oral medication but mostly self-nourished through gastric or
jejunal feeding tube are eligible.
Patients must apply highly effective contraception during and
throughout the study, as well after the final dose of study treatment, as
detailed below:
Men should use an effective method of contraception and not father a
child during the study and for the six-month period after treatment. Men
are recommended to seek advice on conservation of sperm prior to
treatment with paclitaxel as per product label.
Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, must use a highly
effective contraceptive during the study and for at least four weeks after
the final dose of study treatmen
Pt has received previous treatment with any PKB/AKT, mammalian target of rapamycin (mTOR) inhibitors, or PI3K pathway inhibitors.Pt received treatment with taxane as part prior treatment for
metastatic disease.
Pt has symptomatic CNS metastases.Pts with asymptomatic CNS metastases may participate in study. Pt must have
completed any prior local treat for CNS metastases=28 d prior to start study treatment (including radiotherapy) and must be on a stable low dose corticosteroid therapy. Radiosurgery must have been completed at least 14 d prior to start study treatment.
Pt has received wide field radiotherapy=4w or limited field
radiation for palliation=2 w prior to starting study treatment or
who have AE which have not recovered to grade1 or better
from previous chemotherapy treat.
Pt has grade=2 neuropathy, colitis, pneumonitis, elevated
HbA1C, and uncontrolled endocrinopathies from previous treatment.
Pt has had major surgery within 14 d prior to starting treatment or has not recovered from major side effects.
Pt is currently receiving increasing or chronic treatment (>5d) with corticosteroids or immunosuppressive agent. following uses of corticosteroids are permitted: single doses; standard premedication for paclitaxel, topical applications, inhaled
sprays, eye drops,local injections,or<10mg prednisolone or equivalent.
Pt is being treated start of study treatment with any of the following drugs:
Drugs known to be strong/moderate inhibitors or inducers of
isoenzyme cytochrome P4503A4(CYP3A4) including herbal
medications.Drugs with known risk inducing Torsades de Pointes.
Pt is currently receiving warfarin or coumarin-derived anticoagulant,prophylaxis, or otherwise. Therapy with heparin,LMWH,fondaparinux or NOACs is allowed.
Pt has a known hypersensitivity and/or contraindication to
paclitaxel, standard premedication for paclitaxel, or other products
containing Cremophor®.Pt has other concurrent severe and/or uncontrolled medical
conditions that would, in the Dr's judgment, contraindicatept participation
Pt has a known history of HIV infection.
Pt has any following cardiac abnormalities: Symptomatic congestive heart failure within 12 months
screening period ,History of documented congestive heart failure or
documented cardiomyopathy and LVEF<50% as determined by multiple gated acquisition (MUGA) scan orECHO, Myocardial infarction=6m 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 or switched to a different
medication prior to starting study treatment.
Pt has impairment of GI function or GI disease that may
significantly alter the absorption of study treatment.
Patient has a medically documented history of or active major
depressive episode, bipolar disorder (I or II), obsessive-compulsive
disorder, schizophrenia, a history of suicidal attempt or ideation, or
homicidal ideation or active severe personality disorders are not eligible.
Pt has other prior or concurrent malignancy except for the
following: adequately treated basal cell or squamous cell skin cancer, or
other adequately treated in situ cancer, early gastric or GI cancer
resected completely by endoscopy procedures
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method