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

June 6, 2018 updated by: SCRI Development Innovations, LLC

Double-Blind Randomized Phase II Trial of Carboplatin and Pemetrexed With or Without OGX-427 in Patients With Previously Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer (The Spruce Clinical Trial)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

155

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Center
    • Florida
      • Fort Myers, Florida, United States, 33916
        • Florida Cancer Specialists-South
      • Orlando, Florida, United States, 32804
        • Florida Hospital Cancer Insitute
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists-North
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Baptist Hospital East
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Center for Cancer and Blood Disorders
    • Missouri
      • Kansas City, Missouri, United States, 64132
        • Research Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
    • New Jersey
      • Morristown, New Jersey, United States, 07932
        • Hematology-Oncology Associates of Northern NJ
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care, Inc.
    • South Carolina
      • Columbia, South Carolina, United States, 29210
        • South Carolina Oncology Associates
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology - Chattanooga
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology
    • Texas
      • Fort Worth, Texas, United States, 76104
        • The Center for Cancer and Blood Disorders
    • Virginia
      • Newport News, Virginia, United States, 23601
        • Peninsula Cancer Institute
      • Richmond, Virginia, United States, 23230
        • Virginia Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Other Names:
  • apatorsen
Placebo Comparator: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-Free Survival
Time Frame: Every 6 weeks for up to 24 months
Defined as the time (in months) from date of randomization to the date of first observation of progression based on radiological assessment by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, or date of death from any cause, in the absence of progressive disease (PD) or censored at the date of last adequate tumor assessment. Progressive Disease is defined by RECIST v1.1 as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest (nadir) sum while on study (this includes the baseline sum if that is the smallest on study), or the appearance of one or more new lesions.
Every 6 weeks for up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of OGX-427 Versus Placebo Participants With an Objective Response
Time Frame: Every 6 weeks for up to 24 months
Defined as the number of patients with objective evidence of complete or partial response (CR or PR) using RECIST v 1.1. A CR is the complete disappearance of all target lesions. A PR is a decrease in baseline of 30% or more of the diameter(s) of all target lesions.
Every 6 weeks for up to 24 months
Median Overall Survival
Time Frame: Every 6 weeks for up to 41 months
Defined as the time (in months) from date of randomization to date of death from any cause, or censored at the date last known alive.
Every 6 weeks for up to 41 months
Number of Patients With a Treatment-Related Adverse Event as a Measure of Safety.
Time Frame: Weekly during each 21 days cycle and for 30 days after last dose for up to 29 Months
A treatment-related adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
Weekly during each 21 days cycle and for 30 days after last dose for up to 29 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SCRI Development Innovations, LLC

Collaborators

Achieve Life Sciences

Investigators

  • Study Chair: David R. Spigel, M.D., SCRI

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2013

Primary Completion (Actual)

April 19, 2017

Study Completion (Actual)

April 19, 2017

Study Registration Dates

First Submitted

April 8, 2013

First Submitted That Met QC Criteria

April 10, 2013

First Posted (Estimate)

April 11, 2013

Study Record Updates

Last Update Posted (Actual)

June 8, 2018

Last Update Submitted That Met QC Criteria

June 6, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCRI LUN 229

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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