AMG 102 and Erlotinib for Advanced Non-Small Cell Lung Cancer

NCT ID: NCT01233687

Last Updated: 2017-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2014-11-30

Brief Summary

This is a phase I/II study of erlotinib and AMG 102 in previously treated subjects with advanced NSCLC. Subjects will be enrolled with recurrent or progressive advanced stage NSCLC that has been treated with at least one and a maximum of two prior chemotherapy regimens. The Phase I part of the study will enroll 8-16 subjects with the Phase II part enrolling 21-45 subjects.

The Phase I part of the study is designed to determine how safest the combination of AMG 102 and erlotinib is and the recommended dose for the Phase II part. The Phase II part is to determine whether the combination of AMG102 and erlotinib works enough to warrant further interest in this combination.

Detailed Description

While modest improvements have been made in survival and quality of life in patients with advanced NSCLC there is a need to explore new agents and combinations with novel mechanisms of action in an effort to improve clinical outcomes in this patient population. The HGF/c-MET pathway inhibition is a promising novel target in NSCLC. Preclinical evidence support the combined targeting of EGFR and HGF/c-MET pathways in NSCLC as a strategy that may result in enhanced antitumor activity. Inhibition of both HGF/c-Met and EGFR pathways can be accomplished by utilizing the combination of AMG 102 and erlotinib in patients with advanced NSCLC. Therefore, we propose a safety and efficacy, phase I/II clinical trial of the combination in patients with previously treated, advanced NSCLC.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AMG 102 and erlotinib

Combination of AMG 102 and erlotinib

Group Type: EXPERIMENTAL

AMG 102 and erlotinib

Intervention Type: DRUG

Dose Level -2 Dose level -1 Dose Level 0 AMG 102 5 mg/kg 7.5 mg/kg 15 mg/kg Erlotinib 150 mg 150 mg 150 mg

The first cohort of patients in the phase I portion will start at dose level 0 of AMG102.

Interventions

AMG 102 and erlotinib

Dose Level -2 Dose level -1 Dose Level 0 AMG 102 5 mg/kg 7.5 mg/kg 15 mg/kg Erlotinib 150 mg 150 mg 150 mg

The first cohort of patients in the phase I portion will start at dose level 0 of AMG102.

Intervention Type: DRUG

Other Intervention Names

Rilotumumab

Eligibility Criteria

Inclusion Criteria

• Patients with recurrent or progressive advanced stage Non-small cell lung cancer (NSCLC,no SCLC component) who have been treated with at least one and a maximum of two prior chemotherapy regimens for advanced NSCLC. Chemotherapy as part of initial potentially curative therapy (given as part of adjuvant or concomitant chemoradiotherapy) that was completed <1 year counts as 1 prior regimen. Prior erlotinib, other epidermal growth factor receptor (EGFR) TKIs or monoclonal antibodies targeting EGFR are not allowed.

NOTE: Chemotherapy as part of initial potentially curative therapy (given as part of adjuvant or concomitant chemoradiotherapy) that was completed one or more years prior to screening for this study does not count as a prior regimen.

If the tumor is refractory (progressed) after a prior chemotherapy regimen, then that regimen would count. If a prior chemotherapy regimen has been changed due to other reasons than disease progression (e.g. poor tolerance, allergic reaction), then it would not count as a separate prior regimen. A chemotherapy drug added for "maintenance" following disease stabilization or response to a chemotherapy regimen (in the absence of prior disease progression) does not count as a separate prior regimen.

NOTE: Pathology reports documenting the diagnosis of NSCLC are required to be reviewed by the screening physician investigator.

• Measurable disease (RECIST version 1.1) (for phase II part only).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 and life expectancy of ≥ 3 months.

NOTE: For the phase I part of the study, patients with ECOG Performance Status 2 will be excluded.

• Age ≥ 18 years old and ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed.
• Patients must meet the following laboratory criteria (within 14 days prior to study registration):

oHematology: Absolute neutrophil count (ANC) ≥ 1500/mm³ Platelets ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution oBiochemistry: Total Bilirubin within normal institutional limits. AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN), except if there is known hepatic metastasis, wherein transaminases may be ≤ 5 x institutional ULN.

Creatinine clearance 45 ml/min or higher calculated using the Cockcroft-Gault formula. Multiply the number by 0.85 if the patient is female.

Exclusion Criteria

• If patient has history of brain metastases, brain lesions should have been treated with surgery and/or radiation and be stable on repeat imaging and patients should be neurologically stable on a stable or tapering dose of corticosteroids.
• No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a 3-year disease-free interval.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days of the first administration of study treatment and must be willing to use two methods of contraception one of them being a barrier method or abstain from sexual activity during the study and for 6 months after last study drug administration. Sexually active males and their female partners must agree to use two methods of accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study.
• All patients must have given signed, informed consent prior to registration on study.

• Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required. This is due to the unknown effects of AMG102.
• Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent.
• Patients who have mixed tumors with small-cell elements are ineligible.
• Pregnancy or lactation. All females of child-bearing potential must have negative serum or urine pregnancy tests within 7 days prior to starting study treatment.
• Prior treatment of NSCLC with EGFR TKIs or monoclonal antibodies targeting EGFR.
• A serious active infection (>grade 2) within 7 days of enrollment.
• A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• Untreated brain metastases.
• A major surgical procedure or significant traumatic injury within 28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study per inclusion criterion 3.1. In addition, if a patient has not yet recovered from prior minor surgery (such as central venous access device or fine needle aspiration biopsy).
• Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction
• Concurrent or prior (within 7 days of enrollment) anticoagulation therapy, except for the use of low dose coumarin-type anticoagulants or low molecular weight heparin for prophylaxis against central venous catheter thrombosis
• Presence of peripheral edema > Grade 2 (CTCAE version 4).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Ahmad Tarhini

OTHER

Sponsor Role: lead

Responsible Party

Ahmad Tarhini

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ahmad Tarhini, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

10-058

Identifier Type: -

Identifier Source: org_study_id