A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01219699
First received: October 6, 2010
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

This is a first-in-man trial, in which BYL719 will be administered to adult patients with advanced solid tumors, whose tumors have an alteration of the PIK3CA gene and whose disease has progressed despite standard therapy or for whom no standard therapy exists. A combination of BYL719 with fulvestrant will also be investigated in post-menopausal patients with locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene. The single agent MTD dose expansion cohort and the fulvestrant combination MTD dose expansion cohort will also include ER+/HER2- breast cancer patients whose tumors have the wild type PIK3CA gene


Condition Intervention Phase
Advanced Solid Tumors With an Alteration of the PIK3CA Gene
Estrogen Receptor Positive Breast Cancer
Drug: BYL719
Drug: Fulvestrant
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 IA, Multicenter, Open-label Dose Escalation Study of Oral BYL719, in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant [ Time Frame: February 2013 ] [ Designated as safety issue: Yes ]
    Incidence rate of dose limiting toxicities (DLT) (in the first cycle (of 28 days) of each investigated dose level).


Secondary Outcome Measures:
  • Overall safety and tolerability of BYL719 as single agent and in combination with fulvestrant [ Time Frame: April 2014 ] [ Designated as safety issue: Yes ]
    Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0.

  • Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant [ Time Frame: April 2014 ] [ Designated as safety issue: No ]
    plasma concentration-time profiles and derived basic PK parameters of BYL719, including but not limited to AUC0-tlast, AUC0-inf, Cmax, Tmax, CL/F, Vz/F and the terminal half-life (t1/2) and other PK parameters if deemed appropriate.

  • Preliminary efficacy of BYL719 as single agent and in combination with fulvestrant [ Time Frame: April 2014 ] [ Designated as safety issue: No ]
    Objective tumor response rate (ORR), defined as the sum of complete response and partial response as best reported response by RECIST 1.0 criteria (Novartis v2.0 guideline)


Estimated Enrollment: 200
Study Start Date: October 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BYL719
In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene
Drug: BYL719
BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.
Experimental: BYL719 + fulvestrant
In post-menopausal patients with estrogen receptor positive locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene
Drug: Fulvestrant

In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene.

Fulvestrant is an estrogen receptor antagonist, administered by monthly intramuscular injection


  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 solid tumors who have progressed within three months before screening/baseline visit Only patients who have confirmed PIK3CA status (wild type, mutation or amplification) will be allowed for screening (patients participating in the combination arm must be eligible for treatment with fulvestrant)
  • Availability of a representative formalin fixed paraffin embedded tumor tissue sample
  • At least one measurable or non-measurable lesion
  • Age ≥ 18 years
  • World Health Organization (WHO) Performance Status ≤ 2
  • Good organ (hepatic, kidney, BM) function at screening/baseline visit

Exclusion Criteria:

  • Brain metastasis unless treated and free of signs/symptoms attributable to brain metastasis in the absence of corticosteroid therapy (anti-epileptic therapy is allowed).
  • Prior treatment with PI3K, AKT or mTOR inhibitor and failure to benefit
  • Patient with peripheral neuropathy NCI-CTC Grade ≥ 3
  • Patient with diarrhea NCI-CTC Grade ≥ 2
  • Patient with acute or chronic pancreatitis
  • Impaired cardiac function or clinically significant cardiac disease incl. unstable angina pectoris ≤ 3 months prior to starting study drug and Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug.
  • Patients with clinically manifest diabetes mellitus, history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus
  • Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control

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: NCT01219699

Locations
United States, California
University of California San Francisco UCSF Mount Zion
San Francisco, California, United States, 94101
United States, Massachusetts
Massachusetts General Hospital MGH
Boston, Massachusetts, United States, 02114
United States, Tennessee
Vanderbilt Univeristy SC
Nashville, Tennessee, United States, 37232
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4)
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center/University of Texas MD Anderson
Houston, Texas, United States, 77030-4009
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Würzburg, Germany, 97080
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
United Kingdom
Novartis Investigative Site
Oxford, United Kingdom, OX3 7LJ
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: NCT01219699     History of Changes
Other Study ID Numbers: CBYL719X2101, 2010-018782-32
Study First Received: October 6, 2010
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Novartis:
advanced solid tumors
mutation
amplification
wild type
PIK3CA gene
dose-escalation
estrogen receptor positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Estrogens
Fulvestrant
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014