Celecoxib and Docetaxel or Pemetrexed in Treating Patients With Advanced Recurrent Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00520845
• Recruitment Status: Terminated
• First Posted: August 27, 2007
• Results First Posted: October 9, 2014
• Last Update Posted: March 20, 2017
• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Leora Horn, MD, Vanderbilt-Ingram Cancer Center

Tracking Information

• First Submitted Date: August 24, 2007
• First Posted Date: August 27, 2007
• Results First Submitted Date: October 5, 2014
• Results First Posted Date: October 9, 2014
• Last Update Posted Date: March 20, 2017
• Study Start Date: October 2007
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2014)

Median Survival [ Time Frame: 2 years from date of registration ]

Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring (see analysis population description for additional details)

• Original Primary Outcome Measures (submitted: August 24, 2007): Median Survival

Current Secondary Outcome Measures (submitted: October 5, 2014)

• Overall Response Rate [ Time Frame: On-treatment date to date of disease progression (assessed at 6 weeks up to 2 years) ]
  Overall response rate is measured by complete response + partial response. Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD.
• Time to Progression [ Time Frame: 2 years from date of registration ]
  Estimated probable duration from on-study date to date of disease progression, using the Kaplan-Meier method with censoring (see analysis population description for additional details). Disease progression is defined under RECIST v1.1 as >=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.

• Original Secondary Outcome Measures (submitted: August 24, 2007): Time to Progression

Current Other Pre-specified Outcome Measures (submitted: October 5, 2014)

• Effect of Celecoxib on Urinary Metabolites of PGE2, PG12 and Thromboxane [ Time Frame: At 1 year ]
• Changes in Urinary PGE-M and Survival as Assessed by Immunohistochemistry [ Time Frame: At 1 year ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Celecoxib and Docetaxel or Pemetrexed in Treating Patients With Advanced Recurrent Non-Small Cell Lung Cancer
• Official Title: A Phase II Trial of Celecoxib Plus Chemotherapy [Docetaxel or Pemetrexed] in Patients With Previously Treated, "COX Dependent" Recurrent Non-Small Cell Lung Cancer

Brief Summary

RATIONALE: Celecoxib may stop the growth of tumor cells by blocking some of the enzymes need for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving celecoxib together with docetaxel or pemetrexed may kill more tumor cells.

PURPOSE: This phase II trial is studying how well celecoxib given together with docetaxel or pemetrexed works in treating patients with advanced or recurrent non-small cell lung cancer.

Detailed Description

OBJECTIVES:

Primary

• To determine the efficacy of celecoxib when administered with standard chemotherapy comprising docetaxel or pemetrexed disodium in patients with advanced, recurrent non-small cell lung cancer (NSCLC) exhibiting cyclooxygenase (COX) dependence.

Secondary

• To determine the overall response rate and time to progression in patients with COX-dependent recurrent NSCLC treated with celecoxib and docetaxel or pemetrexed disodium.
• To determine the effect of celecoxib on the urinary metabolites of PGE_2 , PGI_2, and thromboxane in patients with COX-dependent recurrent NSCLC.
• To correlate changes in urinary PGE-M and survival with intratumoral expression of COX-2, mPGES, and 15-PGDH as assessed by IHC.

OUTLINE: Patients with no prior taxane exposure receive docetaxel IV over 1 hour on day 1; patients with prior taxane exposure or for whom docetaxel treatment is contraindicated receive pemetrexed disodium IV over 10 minutes on day 1. Treatment with docetaxel or pemetrexed disodium repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral celecoxib twice daily beginning 5-7 days prior to the first docetaxel or pemetrexed disodium infusion and continuing for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and urine sample collection at baseline and periodically during study for biomarker correlative studies. Urine samples are assessed for PGE-M levels. Blood samples are analyzed for serum celecoxib levels, VEGF, endostatin, and cytokine assays.

After completing the last dose of celecoxib, patients are followed at 4-6 weeks and then every 3 months thereafter for up to 2 years from study entry.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lung Cancer

Intervention

• Drug: celecoxib
  600 mg will be taken by mouth twice a day for 6 weeks then 400 mg twice a day for up to a year after chemotherapy is discontinued in the absence of progression.
• Drug: Docetaxel
  75mg/m2 given through a vein over 90 minutes on day 1 of a 3-week cycle
• Drug: pemetrexed disodium
  500 mg/m2 through a vein over 90 minutes on day 1 of a 3 week cycle.
• Other: laboratory biomarker analysis
  Blood collection

Study Arms

Experimental: Treatment Arm

Either docetaxel or pemetrexed given with celecoxib

Interventions:

• Drug: celecoxib
• Drug: Docetaxel
• Drug: pemetrexed disodium
• Other: laboratory biomarker analysis

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 5, 2014): 23
• Original Enrollment (submitted: August 24, 2007): 74
• Actual Study Completion Date: January 2014
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Eligibility Criteria:

• Cytologically or histologically confirmed "COX dependent" non-small cell lung cancer.
• COX dependency is defined by change in urinary PGE-M levels following a "run-in" phase of celecoxib.
• Previous treatment with ≤2 different chemotherapy regimens one of which must have been platinum-based (cisplatin or carboplatin) chemotherapy.
• Age ≥18 years
• ECOG PS 0, 1 or 2.
• Measurable or evaluable disease.
• At least 3 weeks post major surgery, chemotherapy or radiotherapy & recovered from all toxicities.
• Expected survival of at least 2 months.
• CNS metastases permitted provided the patient has adequately recovered from radiotherapy includes stereotactic therapy) or surgery.
• Adequate renal function: serum creatinine ≤1.8 mg/dl &/or CrCl >50 cc/min

Eligibility According to Liver Function:

AST:

</= 1.5 ULN-Docetaxel; </= 2.5 ULN-Pemetrexed (Liver parameters to be used for pemetrexed in the absence of proven or radiographically suspected liver metastases.); </= 5.0 ULN-Pemetrexed (Liver parameters to be used for pemetrexed only in the presence of proven or radiographically suspected liver metastases.)

Alk Phosphatase:

</= 2.5 ULN-Docetaxel; </= 2.5 ULN-Pemetrexed (Liver parameters to be used for pemetrexed in the absence of proven or radiographically suspected liver metastases.); </= 5.0 ULN-Pemetrexed (Liver parameters to be used for pemetrexed only in the presence of proven or radiographically suspected liver metastases.)

Total Bilirubin:

</= 1.5 ULN-Docetaxel; </= 1.5 ULN-Pemetrexed (Liver parameters to be used for pemetrexed in the absence of proven or radiographically suspected liver metastases.); </= 2.5 ULN-Pemetrexed (Liver parameters to be used for pemetrexed only in the presence of proven or radiographically suspected liver metastases.)

• Adequate hematologic function: ANC≥1500/mm3 & platelets ≥100,000/mm3
• Female patients cannot be pregnant and must use contraception if of childbearing age
• Lactating women are excluded.
• Peripheral neuropathy must be CTC grade ≤2
• Patients must not currently be on non-steroidal anti-inflammatory agents or other COX-2 inhibitors (Must be off for at least ≤7 days)
• Written informed consent.

Exclusion Criteria:

• More than two prior chemotherapy regimens for recurrent or relapsed NSCLC.
• COX Independent as defined by change in urinary PGE-M levels following a "run-in" phase of celecoxib.
• Previous treatment with both docetaxel and pemetrexed
• History of greater than grade 2 allergic reaction to celecoxib or any other non-steroid anti-inflammatory agent including aspirin, ibuprofen, or indomethacin.
• History of allergy to compounds containing boron or mannitol.
• History of allergy to sulfonamides.
• Concomitant use of Warfarin, but low dose Coumadin allowed for port prophylaxis
• Recent (past 4 weeks) coronary artery bypass graft (CABG) surgery.
• Inadequate organ function:
• Serum creatinine ≥1.8 mg/dl or a calculated CrCl <45 cc/min.
• AST >1.5 upper limits of normal (ULN); alkaline phosphatase >2.5 ULN; & bilirubin >1.5 ULN
• ANC<1500/mm3 & platelets <100,000/mm3
• Active pregnancy or inability or unwillingness to employ appropriate contraception.
• Small cell carcinoma histology.
• Prior malignancy within 5 years of diagnosis of NSCLC. Exceptions include basal cell or non-metastatic squamous cell carcinomas of the skin, cervical carcinoma in situ or FIGO stage I cervical carcinoma, or other cancer history considered not clinically significant by the principal investigator.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00520845
• Other Study ID Numbers: VICC THO 0730; P30CA068485 ( U.S. NIH Grant/Contract ); VU-VICC-THO-0730; VU-VICC-IRB-070723
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Leora Horn, MD, Vanderbilt-Ingram Cancer Center
• Study Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Leora Horn, MD; Vanderbilt-Ingram Cancer Center

• PRS Account: Vanderbilt-Ingram Cancer Center
• Verification Date: February 2017