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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Yonsei University
Sponsor:
Information provided by (Responsible Party):
Byoung Chul Cho, Yonsei University
ClinicalTrials.gov Identifier:
NCT01527877
First received: January 26, 2012
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Head Neck Cancer Squamous Cell Metastatic
Head Neck Cancer Squamous Cell Recurrent
Drug: BKM120
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • Disease control rate at 8 weeks [ Time Frame: Eight weeks after administration of the drug ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: Every 8 weeks from date of first treatment until date of last treatment up to 24 months ] [ Designated as safety issue: No ]
    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.

  • Toxicity profile [ Time Frame: Every 4 weeks from date of first treatment until date of last treatment up to 24 months ] [ Designated as safety issue: Yes ]

    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.


  • 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 ] [ Designated as safety issue: No ]
    From C1D1 to death

  • 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 ] [ Designated as safety issue: No ]
    From C1D1 until confirmed disease progression or death

  • 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 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]
    From C1D1 until confirmed disease progression.


Estimated Enrollment: 53
Study Start Date: September 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • NVP-BKM120
  • BKM-120

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.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01527877

Contacts
Contact: Byoung Chul Cho, M.D., Ph.D. 82-2-2228-8126 cbc1971@yuhs.ac

Locations
Korea, Republic of
Severance Hospital Recruiting
Seoul, Korea, Republic of
Contact: Byoung Chul Cho, MD    82-2-2228-8126    cbc1971@yuhs.ac   
Principal Investigator: Byoung Chul Cho, M.D., Ph.D.         
Sponsors and Collaborators
Yonsei University
Investigators
Principal Investigator: Byoung Chul Cho, M.D., Ph.D. Yonsei University
  More Information

No publications provided

Responsible Party: Byoung Chul Cho, Assistant professor, Yonsei University
ClinicalTrials.gov Identifier: NCT01527877     History of Changes
Other Study ID Numbers: 2011-0828-001
Study First Received: January 26, 2012
Last Updated: October 4, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Yonsei University:
BKM120
head and neck cancer
squamous cell carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on July 22, 2014