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

NCT ID: NCT00771953

Last Updated: 2019-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2014-12-31

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).

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.

Conditions

Lung Cancer; Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Apricoxib

Apricoxib 400mg once a day

Group Type: EXPERIMENTAL

apricoxib

Intervention Type: DRUG

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

Docetaxel or Pemetrexed

Intervention Type: 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.

Placebo

Placebo once a day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Docetaxel or Pemetrexed

Intervention Type: 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.

Interventions

apricoxib

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

Intervention Type: DRUG

Placebo

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tragara Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin J Edelman

Role: PRINCIPAL_INVESTIGATOR

University of Maryland Greenebaum Cancer Center

Locations

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Mercy Research Institute

Miami, Florida, United States

University of Miami

Miami, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Weill Medical Cornell University

New York, New York, United States

Stony Brook Cancer Center (SUNY)

Stony Brook, New York, United States

Providence Portland Medical Center

Portland, Oregon, United States

Abramson Cancer Center of Uof Pennsylvania

Philadelphia, Pennsylvania, United States

West Virginia University Clinical Trials Research Unit

Morgantown, West Virginia, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 19844858 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 16740761 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15494133 (View on PubMed)

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)

Reference Type: 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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 17522404 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25452446 (View on PubMed)

Other Identifiers

UMGCC 0822

Identifier Type: OTHER

Identifier Source: secondary_id

HP-00043076; 0822GCC

Identifier Type: -

Identifier Source: org_study_id