Study of BKM120 in Advanced Squamous Cell Carcinoma of Head and Neck

NCT ID: NCT01527877

Last Updated: 2012-10-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2014-08-31

Brief Summary

This study is to evaluate disease control rate (DCR) at 8 weeks of BKM120 administered as therapy for patient with recurrent/metastatic head and neck squamous cell carcinoma.

Detailed Description

One promising approach to the treatment of cancer is inhibition or modulating the crucial signal transduction pathway of PI3K-Akt-mTOR. Several PI3K inhibitors are being tested in the clinical trials for cancer treatment but not for the head and neck cancer yet. BKM120 is a specific Pan-class I PI3K inhibitor. We suggest multicenter single arm phase II study to determine anti-tumor effects of BKM120 in patients with recurrent and/or metastatic SCCHN who failed to prior platinum-based chemotherapy regimens.

Conditions

Head Neck Cancer Squamous Cell Metastatic; Head Neck Cancer Squamous Cell Recurrent

Keywords

BKM120; head and neck cancer; squamous cell carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BKM120

Group Type: EXPERIMENTAL

BKM120

Intervention Type: DRUG

Patients will be instructed to take BKM120 orally at a dose of 100 mg with a glass of water once daily, in a fasting state or with a light fat-free meal, and as close as possible to the same time each day. The patient will be dosed on a flat scale of mg/day and not be adjusted to body weight or body surface area. If vomiting occurs no attempt should be made to replace the dose.

• BKM120 should be taken 1-hour following a light meal. Please note that patients must avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pummelos and exotic citrus fruits from 7 days prior to the first dose of study drug and during the entire study treatment period due to potential CYP3A4 interaction. Regular orange juice is allowed.

Interventions

BKM120

Patients will be instructed to take BKM120 orally at a dose of 100 mg with a glass of water once daily, in a fasting state or with a light fat-free meal, and as close as possible to the same time each day. The patient will be dosed on a flat scale of mg/day and not be adjusted to body weight or body surface area. If vomiting occurs no attempt should be made to replace the dose.

• BKM120 should be taken 1-hour following a light meal. Please note that patients must avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pummelos and exotic citrus fruits from 7 days prior to the first dose of study drug and during the entire study treatment period due to potential CYP3A4 interaction. Regular orange juice is allowed.

Intervention Type: DRUG

Other Intervention Names

NVP-BKM120; BKM-120

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed recurrent or metastatic squamous-cell carcinoma of head and neck (SCCHN), except nasopharyngeal carcinoma
• Disease not amenable to curative treatment (surgery or radiation for curative intent)
• 20 years of age or older
• Progressive disease defined as follows

• after one or two prior chemotherapy regimens including platinum-based chemotherapy given for palliation
• within 6 months after concurrent chemoradiotherapy (including induction chemotherapy) delivered as part of primary treatment.
• Life expectancy of at least 12 weeks
• At least one measurable lesion according to the RECIST 1.1 criteria.
• ECOG performance score of 0 ~ 2
• Adequate organ function

• Absolutely Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hemoglobin ≥ 9.0 g/dL
• Serum Creatinine ≤ 1.5 x ULN
• Adequate liver function (total bilirubin ≤ 2.0 x ULN, AST and ALT ≤ 2.0 x ULN or < 5.0 x ULN if liver metastases are present)
• Availability of tissue samples (archival tissue or rebiopsied tissues) for molecular analysis (representative paraffin block or unstained sections from tumor diagnostic specimen are mandatory)
• Patients who have will and ability to comply with the scheduled visits, the treatment plan, laboratory tests and any other trial procedures
• Patient's informed consent

Exclusion Criteria

• Nasopharyngeal carcinoma
• More than two prior lines of chemotherapy in the palliative setting.
• Uncontrolled, untreated brain metastasis Patients with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases ≥ 28 days (must include radiotherapy and/or surgery) and, if on corticosteroid therapy, should be receiving a stable low dose (e.g. dexamethasone 4 mg or equivalent dose of another corticosteroid for at least 14 days before start of study treatment)
• Surgery, chemotherapy or irradiation within 4 weeks of study entry
• Prior treatment with any investigational drug within the preceding 4 weeks
• Concomitant chemotherapy, hormonal therapy or immunotherapy
• Previous or concomitant malignant disease, except adequately treated basal cell cancer of the skin or cervical cancer in situ, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively treated > 5 years prior study entry
• Patient who cannot take the oral drug
• Patient is pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
• Clinically significant psychological disorders including mood and anxiety disorders judged by psychiatry physician
• Patient who have not recovered to grade 1 or better from any adverse events (except alopecia) related to previous antineoplastic therapy before screening procedures are initiated
• Severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.

• Patient has poorly controlled diabetes mellitus (HbA1c> 8 %)
• Patient has history of cardiac dysfunction including history of documented congestive heart failure (New York Heart Association functional classification III-IV) and documented cardiomyopathy
• Patient is currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes. * Active infection, inflammatory bowel disease
• Inadequate liver function (total bilirubin ≥ 2.0 x ULN, AST and ALT ≥ 2.0 x ULN or ≥ 5.0 x ULN if liver metastases are present)

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Byoung Chul Cho

Assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Byoung Chul Cho, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Yonsei University

Locations

Severance Hospital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Byoung Chul Cho, M.D., Ph.D.

Role: CONTACT

Phone: 82-2-2228-8126

Email: cbc1971@yuhs.ac

Facility Contacts

Byoung Chul Cho, MD

Role: primary

References

Kim HR, Kang HN, Yun MR, Ju KY, Choi JW, Jung DM, Pyo KH, Hong MH, Ahn MJ, Sun JM, Kim HS, Kim J, Yoo J, Kim KR, Koh YW, Kim SH, Choi EC, Yoon SO, Shim HS, Paik S, Kim TM, Cho BC. Mouse-human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck. Br J Cancer. 2020 Dec;123(12):1720-1729. doi: 10.1038/s41416-020-01074-2. Epub 2020 Sep 23.

Reference Type: DERIVED

PMID: 32963347 (View on PubMed)

Other Identifiers

2011-0828-001

Identifier Type: -

Identifier Source: org_study_id