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

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.

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.

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)