Phase I Study of Pyrotinib in Patients With HER2-positive Solid Tumors

NCT02500199 | Unknown Phase 1

• 1 other identifier: SHRUS 1001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 10

Brief Summary

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).

Conditions

Breast Cancer; Gastric Cancer; Solid Tumors; NSCLC

Keywords

HER2 positive

Outcome Measures

Primary Outcomes (2)

• Part 1 Maximum Tolerated Dose (MTD)

  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).

  Day 1 to 28 ( Cycle 1)

• Part 2 Overall Response Rate (ORR)

  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).

  up to 24 months after the first dose

Secondary Outcomes (7)

• Maximum plasma concentration(Cmax)

  Up to 3 cycles(each cycle 28 days)

• Time to Cmax

  Up to 3 cycles(each cycle 28 days)

• Terminal half life (t1/2)

  Up to 3 cycles(each cycle 28 days)

• Area under the plasma concentration-time curve

  Up to 3 cycles(each cycle 28 days)

• Volume of distribution(V/F)

  Up to 3 cycles(each cycle 28 days)

Study Arms (1)

Pyrotinib

EXPERIMENTAL

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

Drug: Pyrotinib

Interventions

Pyrotinib DRUG

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.

Also known as: SHR1258

Pyrotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included to participate in this study each patient must:
• be ≥ 18 years of age;
• have an Eastern Cooperative Oncology Group performance status of 0-1 (not declining within past 2 weeks, see Appendix 1);
• have confirmed HER2 gene amplified tumor fluorescence in-situ hybridization (FISH, HER2/cep17 ratio \> 2) or HER2 overexpression (IHC 3+) or documented HER2 gene mutation. Documentation of HER2 status using FDA approved test(s) for HER2 testing specific for HER2 breast and gastric cancer is required prior to screening;
• for part 1:
• Patients with HER2 positive (defined as documented overexpression or amplification or mutation) metastatic breast cancer who have experienced disease progression following at least 2 prior anti-HER2 therapies for metastatic disease that contain trastuzumab with or without pertuzumab, prior T-DM1, or lapatinib therapy is required;
• Patients with HER2 positive metastatic gastric cancer who have disease progression on prior trastuzumab therapy;
• other HER2-positive solid tumors (defined as documented overexpression or amplification or mutation) that have no approved targeted agent as standard of care
• for part 2:
• Patients with HER2 positive metastatic breast cancer who have experienced disease progression after at least 2 prior anti-HER2 therapies for metastatic disease that contain trastuzumab with or without pertuzumab, prior T-DM1, or lapatinib therapy is required;
• Patients with documented HER2 mutated NSCLC whose disease progressed on prior therapy;
• Patients in Part 2 extension must have at least one measurable lesion as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria;
• Left ventricular ejection fraction within institutional limits of normal (by multi gated acquisition scan or echocardiography;
• have the required screening laboratory values including the following parameters:
• Absolute neutrophil count ≥ 1.5×109/L (1,500/mm3);

You may not qualify if:

• Patients who meet any of the criteria listed below will not be eligible for participation in this study. A patient will not be eligible for study participation if:
• is unable or unwilling to swallow pyrotinib;
• has been \< 2 weeks since the last radiotherapy, chemotherapy, hormone therapy, surgery or molecule-target therapy (\< 6 weeks if chemotherapy included nitrosoureas or mitomycin);
• the bone or skin is the only site of disease (for Part 2 extension only);
• has pleural or peritoneal only disease;
• has uncontrolled ≥ grade 2 hypokalemia and hypomagnesemia;
• has had other cancer(s) within 5 years prior to screening with the exception of contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin;
• has active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (patients with a history of CNS metastases or cord compression are allowable if they have been definitively treated and have been clinically stable for at least 4 weeks, and off steroids and anticonvulsants, before first dose of study drug);
• has either QTcF prolongation (\> 470 ms for female and \> 450 ms for male), a known history of QTcF prolongation or Torsade de Pointes; or is on drugs that are required for existing medical conditions and that may result in QT prolongation (e.g., anti-arrhythmic drugs); patients who use medications that have a minimal impact on the QTcF interval in the Arizona-CERT criteria are allowed to participate in this study at Investigator's discretion based on his/her clinical assessment);
• has a significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or ≥ grade 2 diarrhea of any etiology at baseline);
• has participated in any other investigational drug clinical studies within the last 4 weeks;
• is concurrently receiving other anti-tumor therapies at time of study screening visit;
• has an active infection (per Investigator judgment);
• has a history of immunodeficiency including seropositive for human immunodeficiency virus, or has other acquired or congenital immunodeficient disease;
• has evidence of uncontrolled heart disease, including (1) congestive heart failure (New York Heart Association functional classification) of ≥ 2), (2) angina requiring treatment (3) myocardial infarction within the past 12 months, or (4) any clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention;

Sponsors & Collaborators

• Hengrui Therapeutics, Inc.: lead

Study Sites (10)

University of California, Irvine School of Medicine

Orange, California, 92868, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Stomach Neoplasms

Interventions

pyrotinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Junsheng Wang, MD

  Hengrui Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2015
• First Posted: July 16, 2015
• Study Start: June 1, 2015
• Primary Completion: May 1, 2021
• Study Completion: June 1, 2021
• Last Updated: February 1, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)