Phase 1b Trial of BGJ398/BYL719 in Solid Tumors
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| ClinicalTrials.gov Identifier: NCT01928459 |
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Recruitment Status :
Completed
First Posted : August 26, 2013
Last Update Posted : December 9, 2020
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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Brief Summary:
To study the safety and efficacy of the combination of BGJ398 with BYL719 in patients whose tumors express mutations to PIK3CA with or without alterations to FGFR 1-3.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Solid Tumors Metastatic Solid Tumors | Drug: BGJ398 Drug: BYL719 | Phase 1 |
This dose escalation/dose expansion study will evaluate the combination of orally administered BGJ398 in combination with orally administered BYL719. During the dose escalation part, the MTD of the combination will be determined in patients whose advanced or metastatic tumors express mutations to PIK3CA. Once the MTD has been determined, the expansion part will begin. Patients will be addd to one of three arms based on the disease type and genetic changes. Patients with metastatic colorectal cancer are not eligible for participation in the expansion part.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 62 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase Ib, Open-label Study of Oral BGJ398 in Combination With Oral BYL719 in Adult Patients With Select Advanced Solid Tumors |
| Study Start Date : | October 2013 |
| Actual Primary Completion Date : | August 2016 |
| Actual Study Completion Date : | August 2016 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Metastatic breast cancer
Evaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3.
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Drug: BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle. Drug: BYL719 BYL719 will be administered orally once daily on each day of the 28-day cycle. |
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Experimental: Solid tumor arm 1
Patients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA.
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Drug: BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle. Drug: BYL719 BYL719 will be administered orally once daily on each day of the 28-day cycle. |
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Experimental: Solid tumor arm 2
Patients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3
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Drug: BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle. Drug: BYL719 BYL719 will be administered orally once daily on each day of the 28-day cycle. |
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Experimental: Dose escalation
To determine the MTD or RDE of the combination of BGJ398 with BYL719 in patients with advanced or metastastic solid tumors that express mutations to PIK3CA.
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Drug: BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle. Drug: BYL719 BYL719 will be administered orally once daily on each day of the 28-day cycle. |
Primary Outcome Measures :
- Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719 [ Time Frame: Approximately 8 months ]The dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or the recommended dose for expansion (RDE). Safety(incidence and nature of DLTs), pharmacokinetic and pharmacodynamic data will guide dose escalation decisioins.
Secondary Outcome Measures :
- Safety and tolerability of BGJ398/BYL719 combination at the recommended dose for expansion (RDE) [ Time Frame: Every 28 days from baseline visit until end of study visit ]This will be assessed by looking at the number of Adverse Events (AEs), serious AEs (SAEs) changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions and reductions
- Overall response rate [ Time Frame: Every two months from the date of baseline CT scan ]Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719; Overall response rate = complete response + partial response
- Progression free survival [ Time Frame: Every two months from the date of baseline CT scan ]Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719
- Time vs. concentration profile of BGJ398 and BYL719 [ Time Frame: Every 28 days for up to 10 cycles ]Plasma concentration versus time profiles. Plasma PK parameters will be used to characterize the PK profiles of the combination of BGJ398 with BYL719
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Histologically/cytologically confirmed advanced or metastatic solid tumors who have failed standard therapy or for whom no effective standard anti-cancer therapy exists
- Documented PIK3CA mutations in all patients in dose escalation and expansion with or without documented genetic alterations in FGFR depending upon dose expansion cohort (either local or central determination)
- Measurable disease defined by RECIST v1.1
- ECOG performance status of ≤2
Exclusion Criteria:
- Prior PI3Ki or selective FGFR inhibitor treatment (for patients enrolled to expansion part)
- Colorectal cancer (for patients enrolled to expansion part)
- Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting glucose ≥ 140 mg/dL / 7.8 mmol/L, history of clinically significant gestational diabetes mellitus or documented steroid-induced diabetes mellitus
- Use of medications that increase serum levels of phosphorus and/or calcium
- Inorganic phosphorus outside of normal limits
- Total and ionized serum calcium outside of normal limits
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01928459
Locations
| United States, Florida | |
| H. Lee Moffitt Cancer Center & Research Institute Moffitt 4 | |
| Tampa, Florida, United States, 33612 | |
| United States, Michigan | |
| University of Michigan Comprehensive Cancer Center SC | |
| Ann Arbor, Michigan, United States, 48109-0944 | |
| Karmanos Cancer Institute Dept of Onc | |
| Detroit, Michigan, United States, 48201 | |
| United States, Missouri | |
| Washington University School of Medicine Onc Dept | |
| Saint Louis, Missouri, United States, 63110 | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center Onc Dept | |
| New York, New York, United States, 10065 | |
| United States, Tennessee | |
| Vanderbilt University Medical Center Dept of Onc | |
| Nashville, Tennessee, United States, 37232 | |
| United States, Texas | |
| Cancer Therapy & Research Center / UT Health Science Center SC | |
| San Antonio, Texas, United States, 78229 | |
| Australia, Victoria | |
| Novartis Investigative Site | |
| Parkville, Victoria, Australia, 3050 | |
| Belgium | |
| Novartis Investigative Site | |
| Bruxelles, Belgium, 1200 | |
| Canada, Ontario | |
| Novartis Investigative Site | |
| Toronto, Ontario, Canada, M5G 2M9 | |
| France | |
| Novartis Investigative Site | |
| Lyon Cedex, France, 69373 | |
| Novartis Investigative Site | |
| Saint Herblain cedex, France, 44805 | |
| Germany | |
| Novartis Investigative Site | |
| Koeln, Nordrhein-Westfalen, Germany, 50937 | |
| Italy | |
| Novartis Investigative Site | |
| Milano, MI, Italy, 20141 | |
| Novartis Investigative Site | |
| Modena, MO, Italy, 41100 | |
| Korea, Republic of | |
| Novartis Investigative Site | |
| Seoul, Korea, Korea, Republic of, 05505 | |
| Netherlands | |
| Novartis Investigative Site | |
| Amsterdam, Netherlands, 1066 CX | |
| Singapore | |
| Novartis Investigative Site | |
| Singapore, Singapore, 169610 | |
| Spain | |
| Novartis Investigative Site | |
| Sevilla, Andalucia, Spain, 41013 | |
| Novartis Investigative Site | |
| Barcelona, Catalunya, Spain, 08035 | |
| Novartis Investigative Site | |
| Madrid, Spain, 28050 | |
| Switzerland | |
| Novartis Investigative Site | |
| Bellinzona, Switzerland, 6500 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Additional Information:
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01928459 |
| Other Study ID Numbers: |
CBGJ398X2102 |
| First Posted: | August 26, 2013 Key Record Dates |
| Last Update Posted: | December 9, 2020 |
| Last Verified: | August 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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BGJ398 BYL719 advanced solid tumor metastatic breast cancer |
PK3CA FGFR fibroblast growth factor receptor |
Additional relevant MeSH terms:
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Neoplasms Infigratinib Antineoplastic Agents |