0822GCC: Phase 2 Study of Efficacy and Safety of Apricoxib/Placebo With Docetaxel or Pemetrexed in Non-Small Cell Lung Cancer

NCT00771953 | Completed Phase 2 Results DMC

• 2 other identifiers: HP-00043076; 0822GCCUMGCC 0822
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 12

Brief Summary

The primary objective is to determine the anti-tumor activity of the combination of apricoxib + either docetaxel (AP/DC) or pemetrexed (AP/PE) compared with placebo + either docetaxel (P/DC) or pemetrexed (P/PE) as measured by progression free survival in patients with Stage IIIb (pleural effusion)or Stage IV non-small cell lung cancer (NSCLC).

Conditions

Lung Cancer; Non Small Cell Lung Cancer

Keywords

apricoxib; docetaxel; pemetrexed; Stage IIIb or Stage IV

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  For determining progression-free survival, progression was determined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  From the date of randomization until the first date that recurrent or progressive disease is objectively documented.

Study Arms (2)

Apricoxib

EXPERIMENTAL

Apricoxib 400mg once a day

Drug: apricoxib; Drug: Docetaxel or Pemetrexed

Placebo

PLACEBO COMPARATOR

Placebo once a day

Drug: Placebo; Drug: Docetaxel or Pemetrexed

Interventions

apricoxib DRUG

Oral apricoxib tablets will be provided as white or off-white film-coated tablets available in 100mg strength to be taken every day

Apricoxib

Placebo DRUG

Oral placebo tablets will be provided as white or off-white film-coated tablets to be taken every day

Placebo

Docetaxel or Pemetrexed DRUG

Docetaxel 75mg/m2 or Pemetrexed 500mg/m2 given as an IV infusion every 21 days. TheTreating physician will determine chemotherapy drug as per his usual practice.

Apricoxib; Placebo

Eligibility Criteria

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

You may qualify if:

• Pathologically determined stage IV non-small cell lung cancer (NSCLC), including stage IIIb (pleural effusion) (histology or cytology acceptable).
• Documented progression after 1 prior platinum-based chemotherapy. No more than one prior chemotherapy regimen is permitted. Patients may have also received erlotinib (before, after or concurrently with platinum based therapy).
• Measurable disease by RECIST criteria
• Age at least 18 years.
• ECOG performance status of 0-2.
• Required Laboratory Values (within 28 days before randomization) :
• Hb ≥ 9.0gm/dL; transfusions permitted
• ANC ≥ 1500/mm3
• Platelets ≥ 100,000/mm3
• INR ≤ 1.5
• Serum creatinine (Cr) within normal limits for laboratory OR Creatinine clearance greater than or equal to 45 ml/min. 24 hour measured CCr is also acceptable (calculated by the Cockcroft and Gault equation).
• SGOT and SGPT \< 2 X the ULN; if liver metastases are present then must be \< 5 X the ULN
• Bilirubin ≤ Institutional ULN
• Albumin ≥ or equal to 2.5 mg/dl
• May have been treated with anti-EGFR kinase therapy in addition to a platinum based therapy or concurrently with platinum therapy.

You may not qualify if:

• Pregnant or breast feeding
• Known hypersensitivity to apricoxib, docetaxel, other drugs formulated with polysorbate 80, pemetrexed, sulfonamides, aspirin, or other NSAIDs.
• Radiation therapy within 2 weeks or chemotherapy within 3 weeks or non-cytotoxic investigational agents within 3 weeks of initiating study treatment or patients who have not recovered from adverse effects due to agents administered \> 3 weeks prior to initiating study treatment. Screening for urinary PGE-M suppression may begin during this time period.
• Evidence of New York Heart Association class III or greater cardiac disease. History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within 12 months.
• Concurrent severe or uncontrolled medical disease that could compromise the safety of the patient or compromise the ability of the patient to complete the study.
• Known HIV infection or AIDS. Testing not required.
• Symptomatic central nervous system metastases; the patient must be stable after radiotherapy for ≥ 2 weeks. Patients must be off all steroid or antiseizure medications for this indication for ≥ 2 weeks. Patients with CNS metastases that are untreated are eligible if there is no evidence of midline shift, requirement for steroids or antiseizure medications or neurologic symptoms.
• History of upper GI bleeding, ulceration, or perforation within the past 5 years.
• Concurrent use of COX-2 inhibitors or other NSAIDs for 2 days prior to the first dose of study treatment and during study, including aspirin for 7 days prior to the first dose of study treatment and during study.
• Previous COX-2 inhibitor therapy for this diagnosis.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Tragara Pharmaceuticals, Inc.: collaborator

Study Sites (12)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Mercy Research Institute

Miami, Florida, 33133, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Weill Medical Cornell University

New York, New York, 10065, United States

Location

Stony Brook Cancer Center (SUNY)

Stony Brook, New York, 11794, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Abramson Cancer Center of Uof Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

West Virginia University Clinical Trials Research Unit

Morgantown, West Virginia, 26506, United States

Location

Related Publications (8)

• Rao PN, Grover RK. Apricoxib, a COX-2 inhibitor for the potential treatment of pain and cancer. IDrugs. 2009 Nov;12(11):711-22.

  PMID: 19844858 BACKGROUND

• Edelman MJ, Watson D, Wang X, Morrison C, Kratzke RA, Jewell S, Hodgson L, Mauer AM, Gajra A, Masters GA, Bedor M, Vokes EE, Green MJ. Eicosanoid modulation in advanced lung cancer: cyclooxygenase-2 expression is a positive predictive factor for celecoxib + chemotherapy--Cancer and Leukemia Group B Trial 30203. J Clin Oncol. 2008 Feb 20;26(6):848-55. doi: 10.1200/JCO.2007.13.8081.

  PMID: 18281656 BACKGROUND

• Reckamp KL, Krysan K, Morrow JD, Milne GL, Newman RA, Tucker C, Elashoff RM, Dubinett SM, Figlin RA. A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3381-8. doi: 10.1158/1078-0432.CCR-06-0112.

  PMID: 16740761 BACKGROUND

• Murphey LJ, Williams MK, Sanchez SC, Byrne LM, Csiki I, Oates JA, Johnson DH, Morrow JD. Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. Anal Biochem. 2004 Nov 15;334(2):266-75. doi: 10.1016/j.ab.2004.08.019.

  PMID: 15494133 BACKGROUND

• Gitlitz BJ, et al. Apricot-l: Results of a biomarker-based phase II randomized placebocontrolled study of apricoxib in combination with erlotinib in non-small cell lung cancer (NSCLC) patients. Journal of Clinical Oncology 29: 2011 (suppl; abstr 7528)

  BACKGROUND

• Groen HJ, Sietsma H, Vincent A, Hochstenbag MM, van Putten JW, van den Berg A, Dalesio O, Biesma B, Smit HJ, Termeer A, Hiltermann TJ, van den Borne BE, Schramel FM. Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study. J Clin Oncol. 2011 Nov 10;29(32):4320-6. doi: 10.1200/JCO.2011.35.5214. Epub 2011 Oct 11.

  PMID: 21990410 BACKGROUND

• Markowitz SD. Aspirin and colon cancer--targeting prevention? N Engl J Med. 2007 May 24;356(21):2195-8. doi: 10.1056/NEJMe078044. No abstract available.

  PMID: 17522404 BACKGROUND

• Edelman MJ, Tan MT, Fidler MJ, Sanborn RE, Otterson G, Sequist LV, Evans TL, Schneider BJ, Keresztes R, Rogers JS, de Mayolo JA, Feliciano J, Yang Y, Medeiros M, Zaknoen SL. Randomized, double-blind, placebo-controlled, multicenter phase II study of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer. J Clin Oncol. 2015 Jan 10;33(2):189-94. doi: 10.1200/JCO.2014.55.5789. Epub 2014 Dec 1.

  PMID: 25452446 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

apricoxib; Docetaxel; Pemetrexed

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Limitations and Caveats

This study is limited by the relatively low numbers and the hetereogeneity between concurrent treatments (docetaxel vs. pemetrexed). However, in analyses stratified by docetaxel and pemetrexed, results for an affect of apricoxib were still null.

Results Point of Contact

• Title: Michelle Medeiros
• Organization: University of Maryland Baltimore Greenebaum Cancer Center

mmedeiros@umm.edu

410-328-1160

Study Officials

• Martin J Edelman

  University of Maryland Greenebaum Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 10, 2008
• First Posted: October 15, 2008
• Study Start: November 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: December 1, 2014
• Last Updated: October 30, 2019
• Results First Posted: July 22, 2013

Record last verified: 2019-10

Locations

US (12)