A Phase I Study of BKM120 in Adult Chinese Patients With Advanced Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01626209
First received: June 20, 2012
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Advanced Breast Cancer, Advanced Carcinomas With Squamous Cell Histology
Drug: BKM120
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of BKM120, Administered Orally in Adult Chinese Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) [ Time Frame: During Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    An adaptive Bayesian logistic regression model (BLRM) for dose escalation with overdose control will guide the dose escalation. The recommended dose is the one with the highest posterior probablity of DLT in the target interval(16%,33%) among the doses fulfilling the overdose criterion that there is less than 25 % chance of excessive toxicity. A clinical synthesis of the available toxicity information including adverse event that are not DLTs, Pharmacokinetics, Pharmacodynamics, efficacy as well as the recommnendations from the BLRM will be used to determine the dose.


Secondary Outcome Measures:
  • Type, frequency and severity of of Adverse Events (AEs) (based on CTCAE version 4.03 [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
  • Laboratory and vital sign parameters [ Time Frame: 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, ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for Cmax [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for Tmax [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for AUCtlast [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for AUCtau [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for AUCinf [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for AUC%Extrap [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for CL/F [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for Racc [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for T1/2acc [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for Vss/F [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for Rsqadj [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: plasma concentration-time profiles of BKM120 for other PK parameters [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Objective Response Rate (ORR) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Evaluated with CT/MRI according to RECIST criteria (RECIST guidelines version 1.1)

  • Time to Progression (TTP) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Evaluated with CT/MRI according to RECIST criteria (RECIST guidelines version 1.1)


Enrollment: 32
Study Start Date: July 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BKM120 at: 80 and 100mg/day dose levels Drug: BKM120
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).

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01626209

Locations
China, Guangdong
Novartis Investigative Site
Guangzhou, Guangdong, China, 510030
China
Novartis Investigative Site
Beijing, China, 100021
Novartis Investigative Site
Guangzhou, China, 510060
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01626209     History of Changes
Other Study ID Numbers: CBKM120Z2102
Study First Received: June 20, 2012
Last Updated: January 21, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Novartis:
Breast cancer, NSCLC, SCCHN, esophageal cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on October 23, 2014