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

Non Squamous Non Small Cell Lung Cancer Clinical Trial

— Spruce  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01829113
• Other study ID #: SCRI LUN 229
• Status: Completed
• Phase: Phase 2
• Start date: July 2013
• Est. completion date: April 19, 2017

Study information

• Verified date: June 2018
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: April 19, 2017
• Est. primary completion date: April 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Squamous Non Small Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Tennessee Oncology - Chattanooga	Chattanooga	Tennessee
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Florida Cancer Specialists-South	Fort Myers	Florida
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Research Medical Center	Kansas City	Missouri
United States	Baptist Hospital East	Louisville	Kentucky
United States	Hematology-Oncology Associates of Northern NJ	Morristown	New Jersey
United States	Tennessee Oncology	Nashville	Tennessee
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Florida Hospital Cancer Insitute	Orlando	Florida
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Florida Cancer Specialists-North	Saint Petersburg	Florida

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Achieve Life Sciences

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm 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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 May 17. — View Citation

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. Epub 2006 Oct 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of OGX-427 Versus Placebo Participants With an Objective Response	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.	Every 6 weeks for up to 24 months
Secondary	Median Overall Survival	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.	Every 6 weeks for up to 41 months
Secondary	Number of Patients With a Treatment-Related Adverse Event as a Measure of Safety.	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.	Weekly during each 21 days cycle and for 30 days after last dose for up to 29 Months