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

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ClinicalTrials.gov Identifier: NCT01829113
Recruitment Status : Completed
First Posted : April 11, 2013
Results First Posted : June 8, 2018
Last Update Posted : June 8, 2018
Sponsor:
Collaborator:
Achieve Life Sciences
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

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.

Condition or disease Intervention/treatment Phase
Non Squamous Non Small Cell Lung Cancer Drug: OGX-427 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 155 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : July 2013
Actual Primary Completion Date : April 19, 2017
Actual Study Completion Date : April 19, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

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 Name: 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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01829113


Locations
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United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Florida
Florida Cancer Specialists-South
Fort Myers, Florida, United States, 33916
Florida Hospital Cancer Insitute
Orlando, Florida, United States, 32804
Florida Cancer Specialists-North
Saint Petersburg, Florida, United States, 33705
United States, Kentucky
Baptist Hospital East
Louisville, Kentucky, United States, 40207
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Missouri
Research Medical Center
Kansas City, Missouri, United States, 64132
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
United States, New Jersey
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07932
United States, Ohio
Oncology Hematology Care, Inc.
Cincinnati, Ohio, United States, 45242
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
United States, Tennessee
Tennessee Oncology - Chattanooga
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
The Center for Cancer and Blood Disorders
Fort Worth, Texas, United States, 76104
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Virginia Cancer Institute
Richmond, Virginia, United States, 23230
Sponsors and Collaborators
SCRI Development Innovations, LLC
Achieve Life Sciences
Investigators
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Study Chair: David R. Spigel, M.D. SCRI
  Study Documents (Full-Text)

Documents provided by SCRI Development Innovations, LLC:
Study Protocol  [PDF] November 5, 2014
Statistical Analysis Plan  [PDF] May 21, 2015


Publications:

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Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01829113     History of Changes
Other Study ID Numbers: SCRI LUN 229
First Posted: April 11, 2013    Key Record Dates
Results First Posted: June 8, 2018
Last Update Posted: June 8, 2018
Last Verified: June 2018

Keywords provided by SCRI Development Innovations, LLC:
Recurrent Lung Cancer
Stage IV Lung Cancer
OGX-427
Sarah Cannon Research Institute
SCRI
OncoGenex
NSCLC
Non Small Cell Lung Cancer

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors