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

October 4, 2012 updated by: Byoung Chul Cho, Yonsei University

An Open Label, Single Arm, Multicenter Phase II Study of BKM120 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck Who Failed to Respond to Platinum-based Therapy

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

53

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BKM120
Drug: 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.

Other Names:
  • BKM-120
  • NVP-BKM120

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease control rate at 8 weeks
Time Frame: Eight weeks after administration of the drug
The disease control rate (DCR) is defined as the proportion of randomized patients achieving a best overall response of PR or CR or SD, defined by RECIST criteria (version 1.1), relative to the total number of patients in the considered analysis population (ITT).
Eight weeks after administration of the drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: Every 8 weeks from date of first treatment until date of last treatment up to 24 months
Overall objective response rate (ORR) is the best response rate stipulated as complete response (CR) or partial response (PR) (target lesion and tumor response defined according to RECIST guideline version 1.1) and identified as percentage of the confirmed patients.
Every 8 weeks from date of first treatment until date of last treatment up to 24 months
Toxicity profile
Time Frame: Every 4 weeks from date of first treatment until date of last treatment up to 24 months

From C1D1 to 1 months after the last dose adminitration

Overall safety profile verified as relevance of adverse events and laboratory abnormality in the study and grades granted based on (USA National Cancer Center) Common Terminology Criteria for Adverse Events such as the type, frequency and severity (CTCAE), v4.0.
Every 4 weeks from date of first treatment until date of last treatment up to 24 months
Overall survival
Time Frame: Every 8 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months
From C1D1 to death
Every 8 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months
Progression-free survival
Time Frame: Every 8 weeks from date of first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed approximately up to 24 months
From C1D1 until confirmed disease progression or death
Every 8 weeks from date of first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed approximately up to 24 months
Quality of life assessment
Time Frame: Every 4 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months

Quality of life assessment will be performed using FACT-HN& questionnaire

FACT-H&N questionnaire includes physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and head & neck cancer subscale (HNCS).

Patients will be evaluation on baseline, day 1 of every cycle (4 weeks), and end of treatment.
Every 4 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months
Time to progression (TTP)
Time Frame: Every 8 weeks from date of first treatment until the date of first documented progression, assessed approximately up to 24 months
From C1D1 until confirmed disease progression.
Every 8 weeks from date of first treatment until the date of first documented progression, assessed approximately up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yonsei University

Investigators

  • Principal Investigator: Byoung Chul Cho, M.D., Ph.D., Yonsei University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Anticipated)

December 1, 2013

Study Completion (Anticipated)

August 1, 2014

Study Registration Dates

First Submitted

January 26, 2012

First Submitted That Met QC Criteria

February 6, 2012

First Posted (Estimate)

February 7, 2012

Study Record Updates

Last Update Posted (Estimate)

October 8, 2012

Last Update Submitted That Met QC Criteria

October 4, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-0828-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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