Clinical trial NCT01829113: Phase II Trial of Carboplatin and Pemetrexed +/- OGX-427 in Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Squamous Non Small Cell Lung Cancer
Keywords: Recurrent Lung Cancer
Stage IV Lung Cancer
OGX-427
Sarah Cannon Research Institute
SCRI
OncoGenex
NSCLC
Non Small Cell Lung Cancer
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Achieve Life Sciences
First posted: 2013-04-11
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Median Progression-Free Survival
timeFrame: Every 6 weeks for up to 24 months
Secondary outcomes:
measure: Number of OGX-427 Versus Placebo Participants With an Objective Response
timeFrame: Every 6 weeks for up to 24 months
measure: Median Overall Survival
timeFrame: Every 6 weeks for up to 41 months
measure: Number of Patients With a Treatment-Related Adverse Event as a Measure of Safety.
timeFrame: Weekly during each 21 days cycle and for 30 days after last dose for up to 29 Months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists-South
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Insitute
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists-North
state: Florida
city: Louisville
country: United States
facility: Baptist Hospital East
state: Kentucky
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern NJ
state: New Jersey
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology - Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
Study officials:
affiliation: SCRI
name: David R. Spigel, M.D.
role: STUDY_CHAIR
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