Clinical trial NCT01626209: A Phase I Study of BKM120 in Adult Chinese Patients With Advanced Solid Tumors
Official title: A Phase I Study of BKM120, Administered Orally in Adult Chinese Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Breast Cancer, Advanced Carcinomas With Squamous Cell Histology
Keywords: Breast cancer, NSCLC, SCCHN, esophageal cancer
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-06-22
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Dose escalation study with a dose expansion phase, to evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of two dose levels of BKM120 when administered orally.

Detailed description: This is a single arm study, with a starting dose of BKM120 at 80mg/day. Two dose levels: 80mg/day and 100mg /day will be tested in the dose escalation phase. At least 3 patients will be enrolled at each dose level and at least 6 evaluable patients required to be treated at the recommended Phase II dose(RP2D)/MTD dose. After dose escalation the 80mg/day and the 100mg /day dose levels will be expanded to evaluate up to approximately a total of 15 patients each (if 100mg is determined as the RP2D/MTD).

Eligibility criteria: Inclusion Criteria:

* Patients with histologically-confirmed, advanced unresectable breast cancer or advanced carcinoma with squamous cell histology (including NSCLC, SCCHN, and esophageal) who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists
* Patient must provide a representative archival or fresh tumor biopsy for shipping to a Novartis designated laboratory for profiling. Note: one block or ≥ 15 unstained slides is required to determine the PI3K activation status. Whenever possible ≥ 20 unstained slides is preferred.
* Patient has measurable and/or non-measurable disease as per RECIST v1.1 guidelines for solid tumors
* Patient is an adult (female or male) ≥ 18 years of age on the day of consent signature
* Patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2

Exclusion Criteria:

* Patient has received previous treatment with a PI3K inhibitor
* Patient has symptomatic CNS metastases
* Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 14 days prior to the start of study treatment (including radiotherapy and/or surgery). If the patient is receiving ongoing corticosteroid therapy, the following criteria must be met:
* The patient must be receiving a stable or decreasing dose ≤ dexamethasone 4 mg/day or equivalent anti-inflammatory potency of another corticosteroid
* The dose of corticosteroid may not have been escalated for at least 14 days before the start of study treatment
* Patient is currently receiving increasing or chronic treatment with corticosteroids (\>dexamethasone 4 mg or equivalent anti-inflammatory potency of another corticosteroid) or another immunosuppressive agent.
* Note: Topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular) are allowed. Patients with previously treated and asymptomatic brain metastases, are permitted to use corticosteroids as per specific protocol criteria
* Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to starting study treatment is allowed.

  * Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: During Cycle 1 (28 days)
Secondary outcomes:
measure: Type, frequency and severity of of Adverse Events (AEs) (based on CTCAE version 4.03
timeFrame: On a continous basis up to when patient discontinues for progression or until any discontinuation criteria are met e.g AE, patient withdraws consent, Investigator decision; up to 30 days post last study dose
measure: Laboratory and vital sign parameters
timeFrame: Every week cycle 1 & 2 then monthly up to when patient discontinues for progression or until any discontinuation criteria are met e.g AE, patient withdraws consent, Investigator decision,
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for Cmax
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for Tmax
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for AUCtlast
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for AUCtau
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for AUCinf
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for AUC%Extrap
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for CL/F
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for Racc
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for T1/2acc
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for Vss/F
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for Rsqadj
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Pharmacokinetics: plasma concentration-time profiles of BKM120 for other PK parameters
timeFrame: Day 1 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) Day 8 (predose, postdose : 0.5,1,1.5,2,3,4,6,8,24 hr) and Day 28 (predose, postdose: 0.5,1,1.5,2,3,4,6,8,24 hr)
measure: Objective Response Rate (ORR)
timeFrame: Every 8 weeks up to when patient discontinues for progression or until any other discontinuation criteria are met e.g AE, patient withdraws consent, Investigator decision
measure: Time to Progression (TTP)
timeFrame: Every 8 weeks up to when patient discontinues for progression or until any other discontinuation criteria are met e.g AE, patient withdraws consent, Investigator decision
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Beijing
country: China
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: