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NCT Number: NCT01155453

A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 in Selected Advanced Solid Tumor Patients

This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and /or recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid tumors. The focus will be on tumors with RAS/RAF mutations and on triple negative breast cancer.

Both study drugs will be administered once daily orally on a continuous schedule, a treatment cycle is defined as 28 days.

Cohorts of at least 3 and up to a maximum of 6 patients eligible for the dose-determining set will be enrolled per dose combination below the MTD. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment medically unacceptable, dose-limiting toxicity (DLT) in more than 33% of the treated patients.. At least 12 patients will be required at MTD and 6 patients at RP2D level to allow the evaluation of the combination's safety and pharmacokinetics or pharmacodynamics.

Upon declaration of MTD and/or RP2D, patients will be enrolled to an expansion part of the study, to further assess safety, as well as to learn more about the efficacy of the study drug combination.

* Expansion Arm 1 will consist of approximately 15 patients with RAS or BRAF mutant advanced NSCLC * Expansion Arm 2 will consist of approximately 15 patients with RAS or BRAF-mutant ovarian cancer * Expansion Arm 3 will consist of approximately 15 patients with RAS or BRAF-mutant pancreatic cancer

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Key information

Conditions

Advanced and Selected Solid Tumors Breast Diseases Breast Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Neoplasms Neoplasms by Site Pancreatic Diseases Pancreatic Neoplasms Skin Diseases Skin and Connective Tissue Diseases Triple Negative Breast Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Leuven, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • histologically/ cytologically confirmed, advanced non resectable solid tumors
  • Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0

Exclusion criteria

  • Patients with primary Central Nervous System (CNS) tumor or CNS tumor involvement.
  • Clinically manifested diabetes mellitus - Unacceptable ocular/retinal conditions

Other protocol-defined inclusion/exclusion criteria may apply.

Treatment and study plan

BKM120

Drug

GSK1120212

Drug

Primary outcomes

  1. Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212

    Time frame: in average 1 year

Secondary outcomes

  1. Measure the number of Adverse Event and laboratory values that fall outside of pre-determined ranges as a measure of Safety and tolerability of the oral combination of BKM120 and GSK1120212

    Time frame: in average 1 year

  2. Determine the single and multiple dose pharmacokinetics of BKM120 and GSK1120212 in measurement of the plasma concentration profiles of BKM120 and GSK1120212

    Time frame: Assessed during the first Cycle (28 days) of treatment

  3. Preliminary anti-tumor activity of the combination

    Time frame: Assessed every 8 weeks of treatment

  4. Treatment-induced PI3K and MEK/ERK(Mitogen-activated protein kinase /extracellular-signal-regulated kinases) pathway signaling inhibition and evidence of biological activity in tumor and skin

    Time frame: Assessed every 2 weeks during the first cycle, then every 4 weeks

  5. Molecular status (genetic alterations, protein expression and/or activation) of markers related to PI3K and ERK signaling in tumor tissue and blood and investigate their potential relationship to clinical responses

    Time frame: Assessed at baseline (pre-treatment)

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral BKM120 in Combination With Oral GSK1120212 in Adult Patients With Selected Advanced Solid Tumors.

Important dates

Study start
2010
Primary completion
2014
Study completion
2014
First posted
Jul 1, 2010
Registry last updated
Dec 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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