Phase I Study of Pyrotinib in Patients With HER2-positive Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02500199|
Recruitment Status : Active, not recruiting
First Posted : July 16, 2015
Last Update Posted : February 17, 2020
Part 1: to assess the safety and tolerability of pyrotinib and to define the maximum tolerated dose (MTD) of pyrotinib in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive advanced solid tumors (metastatic breast cancer, gastric cancer, or other solid tumors that have no targeted agent as standard of care).
Part 2: to estimate the overall response rate (ORR) for patients with HER2-positive metastatic breast cancer (mBC) and HER2 mutant non-small cell lung cancer (NSCLC) treated at the RP2D (or MTD).
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Gastric Cancer Solid Tumors NSCLC||Drug: Pyrotinib||Phase 1|
This is an open-label, dose escalation study of repeated doses of pyrotinib in patients with HER2-positive advanced solid tumors, including breast cancer, non small cell lung cancer.
Part 1 of the trial is dose escalation and is designed to enroll 3 to 6 patients in each dose group. Adverse events (AEs) will be assessed and monitored throughout the study. Dose-limiting toxicities (DLT) will be assessed from the first dose of study drug through day 28 in the first cycle of treatment.
Part 2 of the trial will consist of two independent arms: arm A for HER2 positive mBC and arm B for NSCLC with documented HER2 mutation will be investigated to further evaluate safety and the preliminary effectiveness and clinical benefits of pyrotinib as a single agent.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Two-part Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Pyrotinib in Patients With HER2-positive Solid Tumors Whose Disease Progressed on Prior HER2 Targeted Therapy|
|Study Start Date :||June 2015|
|Estimated Primary Completion Date :||September 30, 2020|
|Estimated Study Completion Date :||March 2021|
A two-part Phase I, open-label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of pyrotinib in patients with HER2-positive solid tumors whose disease progressed on prior HER2 targeted therapy
Pyrotinib maleate, is provided as yellow, film-coated, immediate release tablets containing pyrotinib maleate at dosage strengths of 80 and 160 mg. Multiple tablets of pyrotinib will be administered daily to achieve targeted doses of pyrotinib: 320 mg, 400 mg, 480 mg, 560 mg and 640 mg. Tablets will be orally administered with water, once daily, 30 min after a meal.
Other Name: SHR1258
- Part 1 Maximum Tolerated Dose (MTD) [ Time Frame: Day 1 to 28 ( Cycle 1) ]to assess safety and tolerability of pyrotinib with a maximum tolerated dose (MTD) of pyrotinib in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive advanced solid tumors (metastatic breast cancer, gastric or other solid tumors with no targeted agent as standard of care).
- Part 2 Overall Response Rate (ORR) [ Time Frame: up to 24 months after the first dose ]to estimate the overall response rate (ORR) for patients with HER2-positive metastatic breast cancer (mBC) and HER2 mutant non-small cell lung cancer (NSCLC) treated at the RP2D (or MTD).
- Maximum plasma concentration(Cmax) [ Time Frame: Up to 3 cycles(each cycle 28 days) ]
- Time to Cmax [ Time Frame: Up to 3 cycles(each cycle 28 days) ]
- Terminal half life (t1/2) [ Time Frame: Up to 3 cycles(each cycle 28 days) ]
- Area under the plasma concentration-time curve [ Time Frame: Up to 3 cycles(each cycle 28 days) ]
- Volume of distribution(V/F) [ Time Frame: Up to 3 cycles(each cycle 28 days) ]
- Plasma Clearance(CL/F) [ Time Frame: Up to 3 cycles(each cycle 28 days) ]
- Progression Free Survival (PFS) [ Time Frame: up to 24 months after the first dose ]
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): NCT02500199
|United States, California|
|University of California, Irvine School of Medicine|
|Orange, California, United States, 92868|
|UC Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Florida|
|Florida Cancer Specialists|
|Sarasota, Florida, United States, 34232|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Michigan|
|Henry Ford Health System|
|Detroit, Michigan, United States, 48202|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|South Texas Accelerated Research Therapeutics|
|San Antonio, Texas, United States, 78229|
|Study Director:||Junsheng Wang, MD||Hengrui Therapeutics, Inc.|