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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01219699
• Collaborator: (none)
• Enrollment: 221
• Locations: 11
• Arms: 2
• Actual Duration (Months): 114.4
• Patients Per Site: 20.1
• Patients Per Site Per Month: 0.2

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
Advanced Solid Tumors With an Alteration of the PIK3CA Gene; Estrogen Receptor Positive Breast Cancer	Drug: BYL719; Drug: Fulvestrant	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 221 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: Oct 5, 2010
• Actual Primary Completion Date: Feb 5, 2015
• Actual Study Completion Date: Apr 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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

3. PK parameters of BYL719 as single agent and in combination with fulvestrant - Cmax. [5 years]

   PK parameter Cmax

4. Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Tmax. [5 years]

   PK parameter Tmax

5. Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - CL/F. [5 years]

   PK parameter CL/F

6. Pharmaconkinetics of BYL719 as single agent and in combination with fulvestrant - Vz/F. [5 years]

   PK parameter Vz/F

7. Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Terminal half-life (t1/2) [5 years]

   PK parameter t1/2

8. 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)

9. Progression-free survival at maximum tolerated dose [5 years]

   PFS at MTD

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01219699
• Other Study ID Numbers: CBYL719X2101; 2010-018782-32
• First Posted: Oct 13, 2010
• Last Update Posted: Sep 22, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: advanced solid tumors; mutation; amplification; wild type; PIK3CA gene; dose-escalation; estrogen receptor positive breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant

Study Results

No Results Posted as of Sep 22, 2020