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

• ClinicalTrials.gov Identifier: NCT00771953
• Recruitment Status: Completed
• First Posted: October 15, 2008
• Results First Posted: July 22, 2013
• Last Update Posted: October 30, 2019
• Sponsor: University of Maryland, Baltimore
• Collaborator: Tragara Pharmaceuticals, Inc.
• Information provided by (Responsible Party): University of Maryland, Baltimore

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Lung Cancer; Non Small Cell Lung Cancer	Drug: apricoxib; Drug: Placebo; Drug: Docetaxel or Pemetrexed	Phase 2

Detailed Description:

Patients diagnosed with advanced non-small cell lung cancer that has not responded to platinum-based chemotherapy are eligible to particvpate in this study.

Current standard treatments for this type of lung cancer are generally not effective in preventing the cancer from growing. The purpose of this study is to see if adding the drug apricoxib to standard chemotherapy is effective in treting NSCLC. Apricoxib is an investigational drug. Investigational means that it is not approved by the Food and Drug Administration (FDA). Laboratory studies suggest that apricoxib may be useful in the treatment of cancer . This is seen particularly when it is combined with chemotherapy drugs. However, this has not been proven in humans.

Laboratory evidence indicates that apricoxib may benefit patients whose disease over-produces a substance called COX-2. COX-2 can be detected in the urine as a substance called PGE-M (prostaglandin E metabolite). It is thought that patients who have a PGE-M level in the urine that decreases by at least half after taking apricoxib may benefit more than patients whose urine PGE-M decreases by less than half after apricoxib.

This study evaluated whether adding apricoxib to standard chemotherapy treatment will improve outcomes in patients with non-small cell lung cancer whose urine PGE-M decreases at least 50% after taking apricoxib. Apricoxib or placebo was added to either docetaxel or pemetrexed treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 0822GCC Randomized, Double-Blind, Placebo-Controlled Multicenter Phase 2 Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in Non-Small Cell Lung Cancer Patients
• Study Start Date: November 2008
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Apricoxib; Apricoxib 400mg once a day	Drug: apricoxib; Oral apricoxib tablets will be provided as white or off-white film-coated tablets available in 100mg strength to be taken every day; Drug: Docetaxel or Pemetrexed; 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.
Placebo Comparator: Placebo; Placebo once a day	Drug: Placebo; Oral placebo tablets will be provided as white or off-white film-coated tablets to be taken every day; Drug: Docetaxel or Pemetrexed; 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.

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival [ Time Frame: From the date of randomization until the first date that recurrent or progressive disease is objectively documented. ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.
• Provide written informed consent and HIPAA authorization and agree to abide by the study restrictions and return for the required assessments.
• Women of child-bearing potential must have negative pregnancy test (serum B-HCG) with a sensitivity of at least 50 mIU/L within 7 days prior to the initiation of treatment and must have used effective contraception (recommended to be two reliable forms of contraception used simultaneously) or must have been sexually abstinent for at least 4 weeks prior to the negative pregnancy test through entry in the study.
• Female patients and male patients with female partners of child-bearing potential must agree to sexual abstinence or to practice effective contraception (recommended to be two reliable forms of contraception used simultaneously). At least one non-hormonal method strongly recommended. Male patients with female sexual partners who are pregnant, or of childbearing potential must agree to use condoms during and for at least 1 month after the last dose of apricoxib.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

United States, California

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

United States, Florida

Mercy Research Institute

Miami, Florida, United States, 33133

University of Miami

Miami, Florida, United States, 33136

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Maryland

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States, 21201

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, New Mexico

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87106

United States, New York

Weill Medical Cornell University

New York, New York, United States, 10065

Stony Brook Cancer Center (SUNY)

Stony Brook, New York, United States, 11794

United States, Oregon

Providence Portland Medical Center

Portland, Oregon, United States, 97213

United States, Pennsylvania

Abramson Cancer Center of Uof Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, West Virginia

West Virginia University Clinical Trials Research Unit

Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

University of Maryland, Baltimore

Tragara Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Martin J Edelman; University of Maryland Greenebaum Cancer Center

More Information

Publications:

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

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.

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.

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.

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)

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT00771953
• Other Study ID Numbers: HP-00043076; 0822GCC; UMGCC 0822 ( Other Identifier: University of Maryland Greenebaum Cancer Center )
• First Posted: October 15, 2008
• Results First Posted: July 22, 2013
• Last Update Posted: October 30, 2019
• Last Verified: October 2019

Keywords provided by University of Maryland, Baltimore:

apricoxib; docetaxel; pemetrexed; Stage IIIb or Stage IV

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Docetaxel; Pemetrexed; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors