A Study of Merestinib (LY2801653) in Japanese Participants With Advanced or Metastatic Cancer

NCT03027284 | Completed Phase 1

• 2 other identifiers: 16330I3O-JE-JSBG
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

The main purpose of this study is to evaluate tolerability of merestinib monotherapy or in combination with other anti-cancer agents in Japanese participants with advanced and/or metastatic cancer.

Conditions

Advanced Cancer; Metastatic Cancer; Biliary Tract Carcinoma; Cholangiocarcinoma; Gall Bladder Carcinoma; Solid Tumor; Non-Hodgkin's Lymphoma

Keywords

Neoplasm

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Merestinib Dose-Limiting Toxicities (DLTs)

  Number of participants with DLTs

  Cycle 1 (Part A = 28 Days or Part B = 21 Days)

Secondary Outcomes (4)

• Pharmacokinetics (PK): Maximum Concentration (Cmax) of Merestinib and its Metabolites

  Predose Cycle 1 Throughout the First 2 Cycles (Part A = 28-Day Cycles, Part B = 21-Day Cycles)

• PK: Area Under the Concentration Time Curve (AUC) of Merestinib and its Metabolites

  Predose Cycle 1 Throughout the First 2 Cycles (Part A = 28-Day Cycles, Part B = 21-Day Cycles)

• Objective Response Rate (ORR): Percentage of Participants With a Complete or Partial Response

  Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated as up to 8 Months)

• Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of Complete Response, Partial Response, and Stable Disease

  Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Estimated as up to 8 Months)

Study Arms (3)

Merestinib (Part A Dose Level 1)

EXPERIMENTAL

Merestinib administered orally. Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met.

Drug: Merestinib

Merestinib (Part A Dose Level 2)

EXPERIMENTAL

Merestinib administered orally. Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met.

Drug: Merestinib

Merestinib + Cisplatin + Gemcitabine (Part B)

EXPERIMENTAL

Merestinib administered orally with cisplatin and gemcitabine administered intravenously (IV). Treatment will continue until disease progression, development of unacceptable toxicity, or other discontinuation criteria are met, but Cisplatin and gemcitabine treatment will be limited to a maximum of 8 cycles.

Drug: Merestinib; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Merestinib DRUG

Administered orally

Also known as: LY2801653

Merestinib (Part A Dose Level 1); Merestinib (Part A Dose Level 2); Merestinib + Cisplatin + Gemcitabine (Part B)

Cisplatin DRUG

Administered IV

Merestinib + Cisplatin + Gemcitabine (Part B)

Gemcitabine DRUG

Administered IV

Also known as: LY188011

Merestinib + Cisplatin + Gemcitabine (Part B)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A: Histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic (solid tumors or non-Hodgkin's lymphoma).
• Part B: Biliary tract carcinoma that is unresectable, recurrent, or metastatic. The participant must not have received prior systemic front-line therapy for metastatic or resectable disease.
• Part A: Measurable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Cheson Criteria.
• Part B: Measurable disease as defined by RECIST v1.1.
• Adequate organ function including hematologic, hepatic and renal.
• Eastern Cooperative Oncology Group (ECOG) scale of 0 or 1.
• Are able to swallow tablets.
• For participants in Part B, a tumor tissue sample is mandatory for biomarker analysis.
• Males must agree to use medically approved barrier contraceptive precautions during the study and for 3 months following the last dose of study drug.
• Females with childbearing potential: Must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug, must have had a negative serum or urine pregnancy test ≤7 days before the first dose of study drug.
• A breastfeeding woman must not be breastfeeding. If a female who stops breastfeeding enters the study, breastfeeding must cease from the day of the first study drug administration until at least 3 months after the last administration.

You may not qualify if:

• Have serious pre-existing medical conditions.
• Have a chronic underlying infection.
• Have symptomatic central nervous system malignancy or metastasis.
• Have an active fungal, bacterial, and/or known viral infection.
• Part B: Have mixed hepatocellular biliary tract carcinoma histology.
• Have liver cirrhosis with a Child-Pugh stage of B or higher, or have received a liver transplant.
• Have a history of congestive heart failure with New York Heart Association (NYHA) class greater than 2, unstable angina, or have recent history of myocardial infarction, transient ischemic attacks, stroke, or arterial or venous vascular disease.
• Have a corrected QT interval \>470 milliseconds as calculated be the Fredericia equation.
• Have a second primary malignancy that, in the judgment of the investigator, and sponsor may affect the interpretation of results.
• Have any evidence of clinically active interstitial lung disease (ILD).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician

Chiba, 277 8577, Japan

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician

Tokyo, 104-0045, Japan

Location

Related Publications (1)

• Doi T, Yamamoto N, Naito Y, Kuboki Y, Koyama T, Piao Y, Tsujimoto N, Asou H, Inoue K, Kondo S. Merestinib monotherapy or in combination for japanese patients with advanced and/or metastatic cancer: A phase 1 study. Cancer Med. 2021 Oct;10(19):6579-6589. doi: 10.1002/cam4.4110. Epub 2021 Sep 9.

  PMID: 34499416 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Cholangiocarcinoma; Gallbladder Neoplasms; Lymphoma, Non-Hodgkin; Neoplasms

Interventions

merestinib; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 19, 2017
• First Posted: January 23, 2017
• Study Start: February 3, 2017
• Primary Completion: June 20, 2019
• Study Completion: March 17, 2020
• Last Updated: May 19, 2020

Record last verified: 2020-05-15

Locations

JP (2)