This clinical study is for patients with advanced non-small cell lung cancer (NSCLC). One half of subjects will be given the experimental drug ARQ 19 tablets together with the approved medicine Tarceva (Erlotinib), while the other half will be given placebo (dummy) tablets together with Tarceva. The study is double blind in its design meaning neither the patient nor the clinical staff participating in the study will known whether they are give the experimental drug ARQ197 or placebo.

Phase 1

Active, not recruiting

• Conditions: on-squamous, non–small-cell lung cancer; MedDRA version: 14.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-022365-10-AT
• Lead Sponsor: Daiichi Sankyo Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-07-27
• Last Update Posted: 24 October 2016

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 988

Inclusion Criteria

1. Male or female at least 18 years of age.

2. Histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage IIIB/IV) non-squamous NSCLC.

3. Measurable disease and documented disease progression following last prior therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version 1.1.

4. Have received one or two prior lines of systemic anti-cancer therapy therapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy. Patients who received only adjuvant treatment will be eligible only if disease progression occurred <6 months after completion of adjuvant therapy. Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued without discontinuation after initiation of a treatment regimen.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Resolution of any toxic effects of prior therapy (including radiotherapy) according to NCI CTCAE, Version 4.0, Grade =1 (with the exception of alopecia and = Grade 2 neuropathy). Subject must have recovered from significant surgery-related complications.

7. Demonstrate adequate bone marrow, liver, and renal functions, defined as:
• ALT, AST, and alkaline phosphatase = 2.5 × upper limit of normal (ULN) in subjects with no liver metastasis and =5.0 x ULN in subjects with liver metastasis.
• Total bilirubin = 1.5 × ULN (= 4 × ULN total and =1.5 × ULN direct bilirubin is acceptable for subjects with Gilbert’s syndrome).
• ANC =1.5 × 10e9/L.
• Platelet count =100 × 10e9/L.
• Hemoglobin =9.0 g/dL (transfusion and/or growth factor support allowed).
• Serum creatinine =1.5 × ULN or creatinine clearance = 60 mL/min.

8. Archival and/or fresh biopsy tissue sample must be available for biomarker determination. The status of the following biomarkers will be collected in this study: EGFR and KRAS mutation status prior to randomization, and MET status post randomization:
a. Previously existing documentation for EGFR and KRAS mutation status from an accredited local laboratory (ie, certified by CLIA, CAP and/or similar agencies) will be accepted.
b. If documented results are not available, then archival and/or fresh tissue biopsy samples (approximately 10 unstained, unbaked, uncharged, paraffinembedded slides) or a tissue block suitable for biomarker analysis must be available.
c. If EGFR and KRAS data from local laboratories are utilized, tissue samples for MET IHC and FISH analysis must be provided to the central lab. Refer to the lab manual for further details on sample requirements.
d. If a subject does not have previous documentation or adequate tissue for EGFR status determination, the subject is not eligible for the study.

9. If of child-bearing/reproductive potential (female or male), must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received.

10. If female and of childbearing potential, must have a negative result of a pregnancy test (serum or urine) within 72 hours prior to initiating study treatment.

11. Must have signed and dated an IEC or IRB approved ICF (Including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests. Subjects must be fully informed about their illness and the investigational nature of the study protocol (includ

Exclusion Criteria

1. Prior therapy with an EGFR inhibitor and/or ARQ 197 (or other known c-MET inhibitor).

2. Receipt of any systemic anti-tumor treatment for NSCLC within 3 weeks prior to randomization.

3. Receipt of palliative radiotherapy within 2 weeks or radiotherapy for curative intent of target lesions within 3 weeks prior to randomization. (Lesions subjected to radiotherapy within 3 weeks prior to randomization may not be used as target lesions.)

4. Major surgical procedure within 3 weeks prior to randomization (brain
metastases treated with sterotactic gamma knife radiosurgery within 3 weeks prior to randomization will be allowed).

5. 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 symptomatic bradycardia (subjects with asymptomatic bradycardia and heart rate above 50 bpm are allowed) or other cardiac arrhythmia defined as =Grade 2 according to NCI 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).

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

7. Need to breastfeed a child during or within 12 weeks of completing the study.

8. Significant gastrointestinal disorder that, in the opinion of the investigator, could interfere with absorption of ARQ 197 and/or erlotinib (eg, Crohn’s disease, small or large bowel resection, malabsorption syndrome).

9. Inability or unwillingness to swallow the complete doses of ARQ 197 or erlotinib.

10. Any known contraindication to treatment with, including hypersensitivity to, ARQ 197 or erlotinib.

11. History of malignancy other than NSCLC within the 5 years prior to randomization, with the exceptions of adequately treated intraepithelial carcinoma of the cervix uteri; prostate carcinoma with a prostate-specific antigen value <0.2 ng/mL; or basal or squamous-cell carcinoma of the skin.

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

13. Any other significant co-morbid condition that, in opinion of the investigator, would impair study participation or cooperation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified