Phase II Trial of Carboplatin and Pemetrexed +/- OGX-427 in Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer

NCT ID: NCT01829113

Last Updated: 2018-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 155 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2017-04-19

Brief Summary

This randomized phase II study will compare the efficacy and safety of the combination of carboplatin and pemetrexed with and without OGX-427 in patients with previously untreated advanced non-squamous NSCLC.

Detailed Description

Modern doublet chemotherapy improves survival in patients with advanced non-small cell lung cancer (NSCLC) compared with supportive care alone, with non-squamous NSCLC patients treated with platinum/pemetrexed living longer than patients treated with platinum/gemcitabine. Despite these advances, poor outcomes with advanced disease warrant exploration of novel drugs with unique mechanisms of action. Preclinical evidence in lung cancer models shows promising antitumor activity with OGX-427 in combination with platinum based therapy or pemetrexed. In this double-blind, placebo-controlled, Phase II study, pemetrexed and carboplatin plus OGX-427 followed by maintenance pemetrexed and OGX-427 will be compared with pemetrexed and carboplatin plus placebo followed by maintenance pemetrexed and placebo in patients with previously untreated advanced non-squamous NSCLC.

Conditions

Non Squamous Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

OGX-427

Three loading doses of OGX-427 at 600mg intravenously (IV) will be administered over 9 days. Following the loading dose period, OGX-427 will be administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle during the Treatment Phase. The Treatment Phase will be followed by a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle.

Group Type: EXPERIMENTAL

OGX-427

Intervention Type: DRUG

Three loading doses of 600mg OGX-427 will be administered intravenously (IV) during a 9 day period. Then 600mg IV OGX-427 will be given weekly on Days 1, 8 and 15 of each 21 day cycle prior to the administration of pemetrexed (500mg/m\^2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle for a maximum of four treatment cycles. Patients who respond to treatment or have stable disease will continue to receive 600 mg IV OGX-427 plus 500mg/m2 IV pemetrexed weekly until toxicity or disease progression.

Placebo

Three loading doses of placebo will be administered intravenously (IV) over 9 days. Following the loading dose period, placebo will be administered IV weekly Days 1, 8 and 15 of each 21 day cycle during the Treatment Phase. The Treatment Phase will be followed by a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Three loading doses of placebo will be administered intravenously (IV) during a 9 day period. Then placebo (IV) will be given weekly on Days 1, 8 and 15 of each 21 day cycle prior to the administration of pemetrexed (500mg/m\^2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle for a maximum of four treatment cycles. Patients who respond to treatment or have stable disease will continue to receive placebo (IV) plus 500mg/m2 IV pemetrexed weekly until toxicity or disease progression.

Interventions

OGX-427

Three loading doses of 600mg OGX-427 will be administered intravenously (IV) during a 9 day period. Then 600mg IV OGX-427 will be given weekly on Days 1, 8 and 15 of each 21 day cycle prior to the administration of pemetrexed (500mg/m\^2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle for a maximum of four treatment cycles. Patients who respond to treatment or have stable disease will continue to receive 600 mg IV OGX-427 plus 500mg/m2 IV pemetrexed weekly until toxicity or disease progression.

Intervention Type: DRUG

Placebo

Three loading doses of placebo will be administered intravenously (IV) during a 9 day period. Then placebo (IV) will be given weekly on Days 1, 8 and 15 of each 21 day cycle prior to the administration of pemetrexed (500mg/m\^2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle for a maximum of four treatment cycles. Patients who respond to treatment or have stable disease will continue to receive placebo (IV) plus 500mg/m2 IV pemetrexed weekly until toxicity or disease progression.

Intervention Type: DRUG

Other Intervention Names

apatorsen

Eligibility Criteria

Inclusion Criteria

1. Histologic or cytologic diagnosis of advanced NSCLC, excluding squamous cell and small cell histology. Tumors with mixed NSCLC histologies are eligible, as long as the predominant histology is not squamous. If small-cell elements are present or not otherwise specified histologically, the patient is not eligible.

2. Metastatic disease (according to American Joint Committee on Cancer (AJCC) staging system, v7.0).

3. No prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy for metastatic disease; previous adjuvant or neoadjuvant therapy for Stage I, II, or III disease is allowed as long as the interval from the end of treatment until disease progression was >12 months.

4. No prior radiation therapy to the whole pelvis or to ≥25% of the total bone marrow area. Other radiation therapy must be completed at least 2 weeks prior to study entry. Must have recovered from acute adverse effects prior to study entry.

5. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

7. Baseline laboratory values as follows:

• Absolute neutrophil count (ANC) ≥1500/μL
• Hemoglobin (Hgb) ≥10 g/dL
• Platelets ≥100,000/μL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ≤3.0 x the upper limit of normal (ULN); 5 x ULN if known hepatic metastases.
• Total bilirubin ≤1.5 x ULN, unless secondary to Gilbert's disease
• Serum creatinine ≤1.5 x ULN. If creatinine is >1.5, calculate creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method:

Glomerular Filtration Rate (GFR) = (140-age) x (weight/kg) x (0.85 if female)/(72 x serum creatinine mg/dL)

8. Fertile male patients willing to use adequate contraceptive measures.

9. Female patients who are not of child-bearing potential, and fertile female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of randomization.

10. Life expectancy ≥ 12 weeks.

11. Must be ≥18 years of age at the time of consent.

12. Willingness and ability to comply with trial and follow-up procedures.

13. Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria

1. Known anaplastic lymphoma kinase (ALK) translocation and epidermal growth factor receptor (EGFR) "activating" mutations where first-line treatment with targeted tyrosine kinase inhibitor therapy is more appropriate.

2. Known central nervous system (CNS) disease other than neurologically stable, treated brain metastases defined as metastasis having no evidence of progression or hemorrhage after treatment and no ongoing requirements for corticosteroids, (e.g., dexamethasone) for at least 2 weeks.

3. Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:

• Unstable angina pectoris
• Congestive heart failure
• Acute myocardial infarction
• Conduction abnormality not controlled with pacemaker or medication
• Significant ventricular or supraventricular arrhythmias (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).

4. Patients currently receiving therapeutic anticoagulation.

5. Pregnant or lactating women.

6. Any serious, active underlying medical condition that would impair the ability of the patient to receive study treatment, such as diabetes mellitus or infection.

7. Unable or unwilling to take folic acid or vitamin B12.

8. Active second malignancy (except non-melanomatous skin or superficial bladder cancer) defined as requiring current need for cancer therapy or at high risk of recurrence (>30%) during the study.

9. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

10. Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.

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

Sponsors

Achieve Life Sciences

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David R. Spigel, M.D.

Role: STUDY_CHAIR

SCRI

Locations

Rocky Mountain Cancer Center

Denver, Colorado, United States

Florida Cancer Specialists-South

Fort Myers, Florida, United States

Florida Hospital Cancer Insitute

Orlando, Florida, United States

Florida Cancer Specialists-North

St. Petersburg, Florida, United States

Baptist Hospital East

Louisville, Kentucky, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Research Medical Center

Kansas City, Missouri, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Hematology-Oncology Associates of Northern NJ

Morristown, New Jersey, United States

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States

South Carolina Oncology Associates

Columbia, South Carolina, United States

Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Peninsula Cancer Institute

Newport News, Virginia, United States

Virginia Cancer Institute

Richmond, Virginia, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SCRI LUN 229

Identifier Type: -

Identifier Source: org_study_id