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

Sponsor
SCRI Development Innovations, LLC (Other)
Overall Status
Completed
CT.gov ID
NCT01829113
Collaborator
Achieve Life Sciences (Industry)
155
Enrollment
16
Locations
2
Arms
45.6
Actual Duration (Months)
9.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
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 :
Jul 1, 2013
Actual Primary Completion Date :
Apr 19, 2017
Actual Study Completion Date :
Apr 19, 2017

Arms and Interventions

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.

    Outcome Measures

    Primary Outcome Measures

    1. Median Progression-Free Survival [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 [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 [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. [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

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

    2. 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.

    3. Life expectancy ≥ 12 weeks.

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

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

    6. 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).

    1. Patients currently receiving therapeutic anticoagulation.

    2. Pregnant or lactating women.

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

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

    5. 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.

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

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Rocky Mountain Cancer Center Denver Colorado United States 80218
    2 Florida Cancer Specialists-South Fort Myers Florida United States 33916
    3 Florida Hospital Cancer Insitute Orlando Florida United States 32804
    4 Florida Cancer Specialists-North Saint Petersburg Florida United States 33705
    5 Baptist Hospital East Louisville Kentucky United States 40207
    6 Center for Cancer and Blood Disorders Bethesda Maryland United States 20817
    7 Research Medical Center Kansas City Missouri United States 64132
    8 Nebraska Methodist Hospital Omaha Nebraska United States 68114
    9 Hematology-Oncology Associates of Northern NJ Morristown New Jersey United States 07932
    10 Oncology Hematology Care, Inc. Cincinnati Ohio United States 45242
    11 South Carolina Oncology Associates Columbia South Carolina United States 29210
    12 Tennessee Oncology - Chattanooga Chattanooga Tennessee United States 37404
    13 Tennessee Oncology Nashville Tennessee United States 37203
    14 The Center for Cancer and Blood Disorders Fort Worth Texas United States 76104
    15 Peninsula Cancer Institute Newport News Virginia United States 23601
    16 Virginia Cancer Institute Richmond Virginia United States 23230

    Sponsors and Collaborators

    • SCRI Development Innovations, LLC
    • Achieve Life Sciences

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT01829113
    Other Study ID Numbers:
    • SCRI LUN 229
    First Posted:
    Apr 11, 2013
    Last Update Posted:
    Jun 8, 2018
    Last Verified:
    Jun 1, 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:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung

    Study Results

    Participant Flow

    Recruitment Details Between August 2013 and February 2015, a total of 155 patients (77 patients on the OGX-427 (apatorsen) arm and 78 patients on the placebo arm) were enrolled and randomized on the study.
    Pre-assignment Detail Subjects were enrolled and randomized in a 1:1 ratio to receive a combination of pemetrexed and carboplatin plus either OGX-427 (apatorsen) or a placebo.
    Arm/Group Title OGX-427 Placebo
    Arm/Group Description 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. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of 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. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.
    Period Title: Overall Study
    STARTED 77 78
    COMPLETED 0 0
    NOT COMPLETED 77 78

    Baseline Characteristics

    Arm/Group Title OGX-427 Placebo Total
    Arm/Group Description 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. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of 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. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression. Total of all reporting groups
    Overall Participants 77 78 155
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    35
    45.5%
    29
    37.2%
    64
    41.3%
    >=65 years
    42
    54.5%
    49
    62.8%
    91
    58.7%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    66
    67
    66
    Sex: Female, Male (Count of Participants)
    Female
    39
    50.6%
    40
    51.3%
    79
    51%
    Male
    38
    49.4%
    38
    48.7%
    76
    49%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    1.3%
    1
    0.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    10
    13%
    3
    3.8%
    13
    8.4%
    White
    67
    87%
    74
    94.9%
    141
    91%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    77
    100%
    78
    100%
    155
    100%

    Outcome Measures

    1. Primary Outcome
    Title Median Progression-Free Survival
    Description 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.
    Time Frame Every 6 weeks for up to 24 months

    Outcome Measure Data

    Analysis Population Description
    All patients who were randomized
    Arm/Group Title OGX-427 Placebo
    Arm/Group Description OGX-427: Three loading doses of OGX-427 at 600mg IV will be administered Days -9 to -1. 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. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients with objective response or stable disease after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression. Placebo: Three loading doses of placebo will be administered IV Days -9 to -1. 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. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients with objective response or stable disease after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.
    Measure Participants 77 78
    Median (95% Confidence Interval) [months]
    6
    4.9
    2. Secondary Outcome
    Title Number of OGX-427 Versus Placebo Participants With an Objective Response
    Description 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.
    Time Frame Every 6 weeks for up to 24 months

    Outcome Measure Data

    Analysis Population Description
    All patients who were randomized.
    Arm/Group Title OGX-427 Placebo
    Arm/Group Description 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. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of 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. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.
    Measure Participants 77 78
    Count of Participants [Participants]
    21
    27.3%
    25
    32.1%
    3. Secondary Outcome
    Title Median Overall Survival
    Description 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.
    Time Frame Every 6 weeks for up to 41 months

    Outcome Measure Data

    Analysis Population Description
    All patients who were randomized.
    Arm/Group Title OGX-427 Placebo
    Arm/Group Description 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. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of 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. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.
    Measure Participants 77 78
    Median (95% Confidence Interval) [Months]
    10.8
    11.8
    4. Secondary Outcome
    Title Number of Patients With a Treatment-Related Adverse Event as a Measure of Safety.
    Description 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.
    Time Frame Weekly during each 21 days cycle and for 30 days after last dose for up to 29 Months

    Outcome Measure Data

    Analysis Population Description
    Randomized patients who received at least one dose of study treatment.
    Arm/Group Title OGX-427 Placebo
    Arm/Group Description 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. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of 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. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients without toxicity or disease progression after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.
    Measure Participants 74 76
    Count of Participants [Participants]
    63
    81.8%
    70
    89.7%

    Adverse Events

    Time Frame Weekly during each 21 days cycle and for 30 days after last dose for up to 29 Months
    Adverse Event Reporting Description Any untoward medical occurrence in a participant regardless of the relationship with 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) v4.0. All-Cause Mortality was assessed in all randomized participants, while Serious and Other (Not Including Serious) Adverse Events was only assessed in participants who received at least one dose of study treatment.
    Arm/Group Title OGX-427 Placebo
    Arm/Group Description OGX-427: Three loading doses of OGX-427 at 600mg IV will be administered Days -9 to -1. 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. OGX-427 will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients with objective response or stable disease after four cycles of therapy will move on to a Maintenance Phase of OGX-427 administered at 600mg IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression. Placebo: Three loading doses of placebo will be administered IV Days -9 to -1. 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. Placebo will be given prior to the administration of pemetrexed (500mg/m2 IV) and carboplatin (AUC 6 IV) on Day 1 of each cycle. A maximum of four treatment cycles will be administered. Patients with objective response or stable disease after four cycles of therapy will move on to a Maintenance Phase of placebo administered IV weekly Days 1, 8 and 15 of each 21 day cycle plus pemetrexed (500mg/m2 IV on Day 1). Patients may remain on maintenance as long as they are benefiting and have no evidence of disease progression.
    All Cause Mortality
    OGX-427 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 56/77 (72.7%) 61/78 (78.2%)
    Serious Adverse Events
    OGX-427 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 35/74 (47.3%) 32/76 (42.1%)
    Blood and lymphatic system disorders
    Anaemia 0/74 (0%) 2/76 (2.6%)
    Haemolytic anaemia 1/74 (1.4%) 0/76 (0%)
    Pancytopenia 0/74 (0%) 2/76 (2.6%)
    Thrombocytopenia 2/74 (2.7%) 0/76 (0%)
    Cardiac disorders
    Atrial fibrillation 2/74 (2.7%) 0/76 (0%)
    Cardiac failure congestive 2/74 (2.7%) 0/76 (0%)
    Cardiac tamponade 0/74 (0%) 1/76 (1.3%)
    Gastrointestinal disorders
    Abdominal pain 0/74 (0%) 1/76 (1.3%)
    Colitis 0/74 (0%) 1/76 (1.3%)
    Constipation 1/74 (1.4%) 1/76 (1.3%)
    Diarrhoea 1/74 (1.4%) 0/76 (0%)
    Dysphagia 1/74 (1.4%) 1/76 (1.3%)
    Gastrointestinal haemorrhage 0/74 (0%) 1/76 (1.3%)
    Intestinal obstruction 0/74 (0%) 1/76 (1.3%)
    Small intestinal obstruction 1/74 (1.4%) 0/76 (0%)
    General disorders
    Asthenia 1/74 (1.4%) 1/76 (1.3%)
    Chest pain 0/74 (0%) 1/76 (1.3%)
    Death 0/74 (0%) 1/76 (1.3%)
    Pyrexia 1/74 (1.4%) 0/76 (0%)
    Hepatobiliary disorders
    Cholecystitis 1/74 (1.4%) 0/76 (0%)
    Cholelithiasis 1/74 (1.4%) 0/76 (0%)
    Infections and infestations
    Bronchitis 0/74 (0%) 1/76 (1.3%)
    Cellulitis 4/74 (5.4%) 0/76 (0%)
    Clostridium difficile colitis 1/74 (1.4%) 0/76 (0%)
    Influenza 0/74 (0%) 1/76 (1.3%)
    Osteomyelitis 1/74 (1.4%) 0/76 (0%)
    Pneumonia 9/74 (12.2%) 8/76 (10.5%)
    Pyelonephritis acute 1/74 (1.4%) 0/76 (0%)
    Urinary tract infection 3/74 (4.1%) 1/76 (1.3%)
    Injury, poisoning and procedural complications
    Acetabulum fracture 1/74 (1.4%) 0/76 (0%)
    Cervical vertebral fracture 0/74 (0%) 1/76 (1.3%)
    Humerus fracture 2/74 (2.7%) 0/76 (0%)
    Multiple fractures 0/74 (0%) 1/76 (1.3%)
    Investigations
    Neutrophil count decreased 1/74 (1.4%) 0/76 (0%)
    Metabolism and nutrition disorders
    Dehydration 3/74 (4.1%) 1/76 (1.3%)
    Failure to thrive 2/74 (2.7%) 0/76 (0%)
    Hypocalcaemia 1/74 (1.4%) 0/76 (0%)
    Hypokalaemia 1/74 (1.4%) 0/76 (0%)
    Hyponatraemia 0/74 (0%) 1/76 (1.3%)
    Malnutrition 0/74 (0%) 1/76 (1.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Non-Hodgkin's lymphoma 0/74 (0%) 1/76 (1.3%)
    Nervous system disorders
    Cerebrovascular accident 1/74 (1.4%) 0/76 (0%)
    Haemorrhage intracranial 1/74 (1.4%) 0/76 (0%)
    Seizure 0/74 (0%) 1/76 (1.3%)
    Subarachnoid haemorrhage 0/74 (0%) 1/76 (1.3%)
    Transient ischaemic attack 1/74 (1.4%) 0/76 (0%)
    Psychiatric disorders
    Confusional state 1/74 (1.4%) 0/76 (0%)
    Mental status changes 1/74 (1.4%) 0/76 (0%)
    Renal and urinary disorders
    Acute kidney injury 3/74 (4.1%) 0/76 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/74 (0%) 1/76 (1.3%)
    Chronic obstructive pulmonary disease 4/74 (5.4%) 1/76 (1.3%)
    Dyspnoea 3/74 (4.1%) 3/76 (3.9%)
    Pleural effusion 1/74 (1.4%) 0/76 (0%)
    Pneumothorax 0/74 (0%) 1/76 (1.3%)
    Respiratory failure 0/74 (0%) 1/76 (1.3%)
    Vascular disorders
    Arteriosclerosis 0/74 (0%) 1/76 (1.3%)
    Deep vein thrombosis 0/74 (0%) 2/76 (2.6%)
    Hypotension 1/74 (1.4%) 1/76 (1.3%)
    Peripheral artery occlusion 1/74 (1.4%) 0/76 (0%)
    Other (Not Including Serious) Adverse Events
    OGX-427 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 72/74 (97.3%) 75/76 (98.7%)
    Blood and lymphatic system disorders
    Anaemia 41/74 (55.4%) 47/76 (61.8%)
    Thrombocytopenia 32/74 (43.2%) 30/76 (39.5%)
    Neutropenia 23/74 (31.1%) 36/76 (47.4%)
    Leukopenia 12/74 (16.2%) 20/76 (26.3%)
    Cardiac disorders
    Atrial fibrillation 5/74 (6.8%) 3/76 (3.9%)
    Tachycardia 2/74 (2.7%) 6/76 (7.9%)
    Eye disorders
    Lacrimation increased 7/74 (9.5%) 4/76 (5.3%)
    Vision blurred 3/74 (4.1%) 5/76 (6.6%)
    Dry eye 2/74 (2.7%) 5/76 (6.6%)
    Gastrointestinal disorders
    Nausea 44/74 (59.5%) 44/76 (57.9%)
    Constipation 37/74 (50%) 34/76 (44.7%)
    Vomiting 28/74 (37.8%) 24/76 (31.6%)
    Diarrhoea 27/74 (36.5%) 18/76 (23.7%)
    Abdominal pain 10/74 (13.5%) 8/76 (10.5%)
    Stomatitis 5/74 (6.8%) 6/76 (7.9%)
    Dysphagia 4/74 (5.4%) 2/76 (2.6%)
    Gastrooesophageal reflux disease 4/74 (5.4%) 4/76 (5.3%)
    Dyspepsia 3/74 (4.1%) 11/76 (14.5%)
    General disorders
    Fatigue 46/74 (62.2%) 50/76 (65.8%)
    Oedema peripheral 17/74 (23%) 15/76 (19.7%)
    Pyrexia 13/74 (17.6%) 11/76 (14.5%)
    Asthenia 12/74 (16.2%) 11/76 (14.5%)
    Chills 11/74 (14.9%) 4/76 (5.3%)
    Chest pain 10/74 (13.5%) 6/76 (7.9%)
    Mucosal inflammation 8/74 (10.8%) 11/76 (14.5%)
    Pain 5/74 (6.8%) 4/76 (5.3%)
    Malaise 2/74 (2.7%) 4/76 (5.3%)
    Infections and infestations
    Urinary tract infection 9/74 (12.2%) 5/76 (6.6%)
    Pneumonia 8/74 (10.8%) 7/76 (9.2%)
    Upper respiratory tract infection 7/74 (9.5%) 11/76 (14.5%)
    Sinusitis 4/74 (5.4%) 8/76 (10.5%)
    Candida infection 2/74 (2.7%) 4/76 (5.3%)
    Bronchitis 1/74 (1.4%) 4/76 (5.3%)
    Conjunctivitis 0/74 (0%) 4/76 (5.3%)
    Injury, poisoning and procedural complications
    Infusion related reaction 8/74 (10.8%) 0/76 (0%)
    Fall 7/74 (9.5%) 4/76 (5.3%)
    Contusion 4/74 (5.4%) 4/76 (5.3%)
    Investigations
    Weight decreased 12/74 (16.2%) 10/76 (13.2%)
    Platelet count decreased 9/74 (12.2%) 10/76 (13.2%)
    Alanine aminotransferase increased 6/74 (8.1%) 7/76 (9.2%)
    Aspartate aminotransferase increased 6/74 (8.1%) 7/76 (9.2%)
    Blood creatinine increased 6/74 (8.1%) 4/76 (5.3%)
    White blood cell count decreased 5/74 (6.8%) 8/76 (10.5%)
    Blood alkaline phosphatase increased 4/74 (5.4%) 3/76 (3.9%)
    Neutrophil count decreased 4/74 (5.4%) 9/76 (11.8%)
    Metabolism and nutrition disorders
    Skin and subcutaneous tissue disorders 35/74 (47.3%) 31/76 (40.8%)
    Decreased appetite 21/74 (28.4%) 20/76 (26.3%)
    Dehydration 14/74 (18.9%) 17/76 (22.4%)
    Hypokalaemia 10/74 (13.5%) 12/76 (15.8%)
    Rash 8/74 (10.8%) 8/76 (10.5%)
    Hypocalcaemia 6/74 (8.1%) 3/76 (3.9%)
    Night sweats 6/74 (8.1%) 1/76 (1.3%)
    Dry skin 4/74 (5.4%) 1/76 (1.3%)
    Hyperglycaemia 4/74 (5.4%) 7/76 (9.2%)
    Hyperhidrosis 3/74 (4.1%) 4/76 (5.3%)
    Hypomagnesaemia 3/74 (4.1%) 5/76 (6.6%)
    Hyponatraemia 3/74 (4.1%) 4/76 (5.3%)
    Rash maculo-papular 3/74 (4.1%) 7/76 (9.2%)
    Musculoskeletal and connective tissue disorders
    Back pain 13/74 (17.6%) 11/76 (14.5%)
    Arthralgia 9/74 (12.2%) 13/76 (17.1%)
    Musculoskeletal pain 6/74 (8.1%) 6/76 (7.9%)
    Muscular weakness 5/74 (6.8%) 4/76 (5.3%)
    Musculoskeletal chest pain 5/74 (6.8%) 4/76 (5.3%)
    Myalgia 5/74 (6.8%) 6/76 (7.9%)
    Pain in extremity 5/74 (6.8%) 8/76 (10.5%)
    Bone pain 3/74 (4.1%) 8/76 (10.5%)
    Muscle spasms 3/74 (4.1%) 5/76 (6.6%)
    Nervous system disorders
    Dizziness 16/74 (21.6%) 16/76 (21.1%)
    Paraesthesia 9/74 (12.2%) 6/76 (7.9%)
    Dysgeusia 6/74 (8.1%) 10/76 (13.2%)
    Headache 5/74 (6.8%) 15/76 (19.7%)
    Neuropathy peripheral 4/74 (5.4%) 7/76 (9.2%)
    Psychiatric disorders
    Insomnia 12/74 (16.2%) 18/76 (23.7%)
    Anxiety 9/74 (12.2%) 9/76 (11.8%)
    Depression 3/74 (4.1%) 9/76 (11.8%)
    Confusional state 2/74 (2.7%) 4/76 (5.3%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 26/74 (35.1%) 21/76 (27.6%)
    Cough 13/74 (17.6%) 31/76 (40.8%)
    Chronic obstructive pulmonary disease 7/74 (9.5%) 2/76 (2.6%)
    Productive cough 7/74 (9.5%) 4/76 (5.3%)
    Epistaxis 5/74 (6.8%) 8/76 (10.5%)
    Haemoptysis 5/74 (6.8%) 2/76 (2.6%)
    Oropharyngeal pain 4/74 (5.4%) 3/76 (3.9%)
    Pleural effusion 4/74 (5.4%) 1/76 (1.3%)
    Wheezing 4/74 (5.4%) 1/76 (1.3%)
    Sinus congestion 3/74 (4.1%) 4/76 (5.3%)
    Dyspnoea exertional 2/74 (2.7%) 5/76 (6.6%)
    Nasal congestion 2/74 (2.7%) 8/76 (10.5%)
    Rhinorrhoea 2/74 (2.7%) 6/76 (7.9%)
    Upper-airway cough syndrome 2/74 (2.7%) 4/76 (5.3%)
    Vascular disorders
    Hypotension 9/74 (12.2%) 10/76 (13.2%)
    Flushing 4/74 (5.4%) 1/76 (1.3%)
    Hot flush 4/74 (5.4%) 0/76 (0%)
    Hypertension 4/74 (5.4%) 15/76 (19.7%)
    Deep vein thrombosis 1/74 (1.4%) 6/76 (7.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Senior Director, Regulatory Science
    Organization Sarah Cannon Development Innovations
    Phone 844-710-6157
    Email CANN.InnovationsMedical@sarahcannon.com
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT01829113
    Other Study ID Numbers:
    • SCRI LUN 229
    First Posted:
    Apr 11, 2013
    Last Update Posted:
    Jun 8, 2018
    Last Verified:
    Jun 1, 2018