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

Phase 2

• Conditions: Head Neck Cancer Squamous Cell Metastatic; Head Neck Cancer Squamous Cell Recurrent
• Interventions: Drug: BKM120

• Registration Number: NCT01527877
• Lead Sponsor: Yonsei University

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.

Study Timeline

• Study First Submitted: 2012-01-26
• Study First Submitted QC: 2012-02-06
• Study First Posted: 2012-02-07
• Study Start: 2012-09
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-04
• Last Update Posted: 2012-10-08
• Primary Completion: 2013-12
• Study Completion: 2014-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 53

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BKM120	BKM120	-

Primary Outcome Measures

Name	Time	Method
Disease control rate at 8 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	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.
Toxicity profile	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.
Overall survival	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
Progression-free survival	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
Quality of life assessment	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.
Time to progression (TTP)	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.

Trial Locations

Locations (1)

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of