A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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
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Outcome Measures
Primary Outcome Measures
- Incidence rate of dose limiting toxicities (DLT). [5 years]
MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant.
Secondary Outcome Measures
- Overall safety and tolerability of BYL719 as single agent and in combination with fulvestrant [10 years]
Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0.
- PK parameters of BYL719 as single agent and in combination with fulvestrant - AUC-tlast and AUC0-inf. [5 years]
PK parameters AUC-tlast and AUC0-inf
- PK parameters of BYL719 as single agent and in combination with fulvestrant - Cmax. [5 years]
PK parameter Cmax
- Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Tmax. [5 years]
PK parameter Tmax
- Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - CL/F. [5 years]
PK parameter CL/F
- Pharmaconkinetics of BYL719 as single agent and in combination with fulvestrant - Vz/F. [5 years]
PK parameter Vz/F
- Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Terminal half-life (t1/2) [5 years]
PK parameter t1/2
- Preliminary efficacy of BYL719 as single agent and in combination with fulvestrant by measuring ORR. [5 years]
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)
- Progression-free survival at maximum tolerated dose [5 years]
PFS at MTD
Eligibility Criteria
Criteria
Inclusion Criteria:
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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)
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Availability of a representative formalin fixed paraffin embedded tumor tissue sample
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At least one measurable or non-measurable lesion
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Age ≥ 18 years
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World Health Organization (WHO) Performance Status ≤ 2
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Good organ (hepatic, kidney, BM) function at screening/baseline visit
Exclusion Criteria:
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Brain metastasis unless treated and free of signs/symptoms attributable to brain metastasis in the absence of corticosteroid therapy (anti-epileptic therapy is allowed).
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Prior treatment with PI3K, AKT or mTOR inhibitor and failure to benefit
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Patient with peripheral neuropathy NCI-CTC Grade ≥ 3
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Patient with diarrhea NCI-CTC Grade ≥ 2
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Patient with acute or chronic pancreatitis
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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.
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Patients with clinically manifest diabetes mellitus, history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus
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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
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | UCSF Medical Center | San Francisco | California | United States | 94143 |
2 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
3 | Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4) | Nashville | Tennessee | United States | 37203 |
4 | Vanderbilt Univeristy SC | Nashville | Tennessee | United States | 37232 |
5 | MD Anderson Cancer Center/University of Texas MD Anderson | Houston | Texas | United States | 77030-4009 |
6 | Novartis Investigative Site | Essen | Germany | 45147 | |
7 | Novartis Investigative Site | Wuerzburg | Germany | 97080 | |
8 | Novartis Investigative Site | Amsterdam | Netherlands | 1066 CX | |
9 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08035 |
10 | Novartis Investigative Site | Hospitalet de LLobregat | Catalunya | Spain | 08907 |
11 | Novartis Investigative Site | Oxford | United Kingdom | OX3 7LJ |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CBYL719X2101
- 2010-018782-32