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A Phase II Trial of Celecoxib Plus Chemotherapy [Docetaxel or Pemetrexed] in Patients With Previously Treated, "COX Dependent" Recurrent Non-Small Cell Lung Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lung Cancer

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Trial Information

A Phase II Trial of Celecoxib Plus Chemotherapy [Docetaxel or Pemetrexed] in Patients With Previously Treated, "COX Dependent" Recurrent Non-Small Cell Lung Cancer


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.

Inclusion 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:

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

Alk Phosphatase:

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

Total Bilirubin:

in the absence of proven or radiographically suspected liver metastases.); 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.

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Median survival

Outcome Time Frame:

two years from date of registration

Safety Issue:

No

Principal Investigator

Leora Horn, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

VICC THO 0730

NCT ID:

NCT00520845

Start Date:

October 2007

Completion Date:

December 2019

Related Keywords:

  • Lung Cancer
  • 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
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Vanderbilt-Ingram Cancer Center - Cool SpringsNashville, Tennessee  37064
Vanderbilt-Ingram Cancer Center at FranklinNashville, Tennessee  37064