Clinical trial NCT01527877: Study of BKM120 in Advanced Squamous Cell Carcinoma of Head and Neck
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Head Neck Cancer Squamous Cell Metastatic
Head Neck Cancer Squamous Cell Recurrent
Keywords: BKM120
head and neck cancer
squamous cell carcinoma
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2012-02-07
Enrollment: 53
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Disease control rate at 8 weeks
timeFrame: Eight weeks after administration of the drug
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Every 8 weeks from date of first treatment until date of last treatment up to 24 months
measure: Toxicity profile
timeFrame: Every 4 weeks from date of first treatment until date of last treatment up to 24 months
measure: Overall survival
timeFrame: Every 8 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months
measure: Progression-free survival
timeFrame: 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
measure: Quality of life assessment
timeFrame: Every 4 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months
measure: Time to progression (TTP)
timeFrame: Every 8 weeks from date of first treatment until the date of first documented progression, assessed approximately up to 24 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
affiliation: Yonsei University
name: Byoung Chul Cho, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.