Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Metastatic Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 2 Randomized Open-label Study of Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Previously Treated KRAS Mutation Positive Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01395758
• Other study ID #: ARQ 197-218
• Status: Completed
• Phase: Phase 2
• First received: July 1, 2011
• Last updated: March 5, 2018
• Start date: July 2011
• Est. completion date: August 2016

Study information

• Verified date: March 2018
• Source: ArQule
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate progression-free survival among subjects with KRAS mutation positive Non-Small Cell Lung Cancer (NSCLC) treated with erlotinib plus tivantinib (ARQ 197) compared to single agent chemotherapy.

Description:

This is a randomized, open-label Phase 2 study designed to compare treatment with erlotinib plus tivantinib (ARQ 197) versus single agent chemotherapy in subjects with previously treated KRAS mutation positive NSCLC. Eligible subjects are randomly assigned to receive erlotinib plus tivantinib or one of three (based on Investigator's choice) single-agent chemotherapy agents including pemetrexed, docetaxel, or gemcitabine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provide signed and dated informed consent prior to study-specific screening procedures

2. Male or female at least 18 years of age

3. Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IVA/IVB) NSCLC

4. Documented KRAS mutation positive status (per Lung Cancer Mutation Consortium [LCMC] guidelines; see www.golcmc.com)

5. At least one prior chemotherapy regimen for advanced NSCLC

6. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version 1.1

7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

8. Male or female subjects of child-producing potential must agree to use double barrier contraception, oral contraceptives or avoidance of pregnancy measures during the study and for 90 days after the last day of treatment

9. Females of childbearing potential must have a negative serum pregnancy test

10. Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 × upper limit of normal (ULN) or = 5 × ULN with metastatic liver disease

11. Total bilirubin = 1.5 × ULN

12. Serum creatinine = 1.5 × ULN

13. Absolute neutrophil count (ANC) = 1.5 x 10^9/L

14. Platelets = 100 x 10^9/L

15. Hemoglobin = 10 g/dL (transfusion is allowed at least 7 days prior to randomization)

16. Subjects must agree to allow testing for c-Met status if archival and/or fresh tissue biopsy samples are available.

Exclusion Criteria:

1. Previous receipt of erlotinib or other epidermal growth factor receptor (EGFR) inhibitors

2. Previous receipt of any c-MET inhibitor (a receptor tyrosine kinase) or other c-MET-targeted therapy, including ARQ 197, MetMab, crizotinib

3. Prior receipt of chemotherapy agent selected for administration in this study (e.g., if subject was treated with gemcitabine, he is not eligible to receive gemcitabine in this study but eligible to receive pemetrexed or docetaxel).

4. Inability or unwillingness to receive ARQ 197, erlotinib, docetaxel, gemcitabine, and/or pemetrexed including contraindications, hypersensitivity, or prior administration

5. Receipt of any anti-tumor treatment for NSCLC within 3 weeks (2 weeks for radiotherapy) prior to randomization

6. Pregnant or breastfeeding

7. Significant gastrointestinal disorder that could, in the opinion of the Investigator, interfere with the absorption of ARQ 197 and/or erlotinib

8. Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation

9. Other malignancies within the last three years, with the exception of adequately treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a prostate-specific antigen (PSA) value < 0.2 ng/mL or basal or squamous cell carcinoma of the skin

10. Known human immunodeficiency virus (HIV), or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

11. Major surgical procedure within 4 weeks prior to randomization

12. History of cardiac disease: Congestive heart failure defined as Class II to IV per New York Heart Association classification; Active coronary artery disease; Previously diagnosed bradycardia or other cardiac arrhythmia defined as = Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; Myocardial infarction that occurred within 6 months prior to study entry (myocardial infarction that occurred > 6 months prior to study entry is permitted)

13. Clinically unstable central nervous system metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by MRI or CT scan within 4 weeks of randomization and have central nervous system [CNS] metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications)

14. Known EGFR-mutation positive status

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Non-Small Cell Lung Cancer

Intervention

Drug:
• ARQ 197 plus erlotinib
Eligible subjects will be randomly assigned to receive erlotinib plus ARQ 197.
• Pemetrexed, docetaxel or gemcitabine
Investigator's choice of a single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to the approved label.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ArQule

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) Among Subjects With KRAS Mutation Positive NSCLC (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Single Agent Chemotherapy.	Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) criteria as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or progression of existing non-target lesions are also considered progression.	Date of randomization until disease progression per RECIST (v 1.1) or death from any cause, whichever came first, assessed up to 24 months.
Secondary	Overall Survival (OS) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.	OS is calculated from the date of randomization until death from any cause.	Date of randomization to the date of death from any cause, assessed up to 24 months
Secondary	Objective Response Rate (ORR) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.	Per RECIST v1.1, Complete Response (CR) = disappearance of all lesions and Partial Response (PR) = at least 30% decrease in the sum of diameters of target lesions. ORR = (CR+PR)/# subjects.	Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months
Secondary	ORR Among Subjects in the Crossover Period Treated With Erlotinib Plus Tivantinib	Per RECIST v1.1, CR = disappearance of all lesions and PR = at least 30% decrease in the sum of diameters of target lesions. ORR = (CR+PR)/# subjects.	Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months.