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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lung Cancer, Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: apricoxib
* Drug: Placebo
* Drug: Docetaxel or Pemetrexed


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apricoxib<br>Apricoxib 400mg once a day | Drug: apricoxib<br>* Oral apricoxib tablets will be provided as white or off-white film-coated tablets available in 100mg strength to be taken every day<br>Drug: Docetaxel or Pemetrexed<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Placebo once a day | Drug: Placebo<br>* Oral placebo tablets will be provided as white or off-white film-coated tablets to be taken every day<br>Drug: Docetaxel or Pemetrexed<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apricoxib, docetaxel, pemetrexed, Stage IIIb or Stage IV