Clinical trial NCT00520845: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IV non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IIIA non-small cell lung cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-08-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Median Survival
timeFrame: 2 years from date of registration
Secondary outcomes:
measure: Overall Response Rate
timeFrame: On-treatment date to date of disease progression (assessed at 6 weeks up to 2 years)
measure: Time to Progression
timeFrame: 2 years from date of registration
Other outcomes:
measure: Effect of Celecoxib on Urinary Metabolites of PGE2, PG12 and Thromboxane
timeFrame: At 1 year
measure: Changes in Urinary PGE-M and Survival as Assessed by Immunohistochemistry
timeFrame: At 1 year
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Franklin
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Leora Horn, MD
role: STUDY_CHAIR
References: