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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by SCRI Development Innovations, LLC
Sponsor:
Collaborator:
OncoGenex Pharmaceuticals
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01829113
First received: April 8, 2013
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Non Squamous Non Small Cell Lung Cancer
Drug: OGX-427
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Progression-Free Survival [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
    To determine whether OGX-427 plus carboplatin/pemetrexed therapy shows a progression-free survival advantage versus carboplatin/pemetrexed


Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
    To compare overall response rate in each treatment arm

  • Safety of the regimen [ Time Frame: Continuous review ] [ Designated as safety issue: Yes ]
    To compare the safety/toxicity of the combination of OGX-427 with carboplatin/pemetrexed versus placebo with carboplatin/pemetrexed. Treatment related toxicities will be assessed using Common Terminology Criteria for Adverse Events v4.0

  • Overall Survival [ Time Frame: Time from randomization until death ] [ Designated as safety issue: No ]
    To compare overall survival in each treatment arm


Other Outcome Measures:
  • Serum levels of Hsp27 [ Time Frame: Every cycle (3 weeks) ] [ Designated as safety issue: No ]
    To evaluate the effect of treatment with OGX-427 on serum Hsp27 levels

  • Biomarkers in Archival Tissue [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    To evaluate the correlation of biomarkers from archived tissue samples with clinical outcomes by assessing protein expression and a panel of genes utilizing an assay


Estimated Enrollment: 155
Study Start Date: July 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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. 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 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 Comparator: 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. 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 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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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. Recurrent or Stage IV disease (according to American Joint Committee on Cancer (AJCC) staging system, v7.0).
  3. No prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy; adjuvant therapy is allowed as long as the interval from end of adjuvant therapy until disease progression was >12 months.
  4. No prior radiation therapy to the whole pelvis or to ≥25% of the total bone marrow area. Radiation therapy must be completed at least 2 weeks prior to randomization. Must have recovered from acute adverse effects prior to randomization.
  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 (PS) 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 (>350%) 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01829113

Contacts
Contact: Sarah Cannon Research Institute (SCRI) 877-691-7274 asksarah@scresearch.net

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

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01829113     History of Changes
Other Study ID Numbers: SCRI LUN 229
Study First Received: April 8, 2013
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

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:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on August 27, 2014