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

NCT01829113 | Completed Phase 2 Results

• 1 other identifier: SCRI LUN 229
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 16

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.

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

Outcome Measures

Primary Outcomes (1)

• Median Progression-Free Survival

  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 Outcomes (3)

• Number of OGX-427 Versus Placebo Participants With an Objective Response

  Every 6 weeks for up to 24 months

• Median Overall Survival

  Every 6 weeks for up to 41 months

• 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

Study Arms (2)

OGX-427

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

OGX-427 DRUG

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.

Also known as: apatorsen

OGX-427

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Metastatic disease (according to American Joint Committee on Cancer (AJCC) staging system, v7.0).
• 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.
• 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.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• 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)
• Fertile male patients willing to use adequate contraceptive measures.

You may not qualify if:

• 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.
• 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.
• 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).
• Patients currently receiving therapeutic anticoagulation.
• Pregnant or lactating women.
• Any serious, active underlying medical condition that would impair the ability of the patient to receive study treatment, such as diabetes mellitus or infection.
• Unable or unwilling to take folic acid or vitamin B12.
• 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.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
• Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Achieve Life Sciences: collaborator

Study Sites (16)

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists-South

Fort Myers, Florida, 33916, United States

Location

Florida Hospital Cancer Insitute

Orlando, Florida, 32804, United States

Location

Florida Cancer Specialists-North

St. Petersburg, Florida, 33705, United States

Location

Baptist Hospital East

Louisville, Kentucky, 40207, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Hematology-Oncology Associates of Northern NJ

Morristown, New Jersey, 07932, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23230, United States

Location

Related Publications (6)

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Gronberg BH, Bremnes RM, Flotten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollali T, Wammer F, Aasebo U, Sundstrom S. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. doi: 10.1200/JCO.2008.20.9114. Epub 2009 May 11.

  PMID: 19433683 BACKGROUND

• Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. doi: 10.1200/JCO.2007.15.0375. Epub 2008 May 27.

  PMID: 18506025 BACKGROUND

• Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.

  PMID: 12860938 BACKGROUND

• Wu R, Kausar H, Johnson P, Montoya-Durango DE, Merchant M, Rane MJ. Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex. J Biol Chem. 2007 Jul 27;282(30):21598-608. doi: 10.1074/jbc.M611316200. Epub 2007 May 17.

  PMID: 17510053 BACKGROUND

• Zheng C, Lin Z, Zhao ZJ, Yang Y, Niu H, Shen X. MAPK-activated protein kinase-2 (MK2)-mediated formation and phosphorylation-regulated dissociation of the signal complex consisting of p38, MK2, Akt, and Hsp27. J Biol Chem. 2006 Dec 1;281(48):37215-26. doi: 10.1074/jbc.M603622200. Epub 2006 Oct 2.

  PMID: 17015449 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

apatorsen

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Results Point of Contact

• Title: Senior Director, Regulatory Science
• Organization: Sarah Cannon Development Innovations

CANN.InnovationsMedical@sarahcannon.com

844-710-6157

Study Officials

• David R. Spigel, M.D.

  SCRI

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2013
• First Posted: April 11, 2013
• Study Start: July 1, 2013
• Primary Completion: April 19, 2017
• Study Completion: April 19, 2017
• Last Updated: June 8, 2018
• Results First Posted: June 8, 2018

Record last verified: 2018-06

Locations

US (16)