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Randomized Phase II Trial of Sequential Versus Concurrent Docetaxel and PS-341 (NSC 681239, IND 58,443) in Previously Treated Non-Small Cell Lung Cancer

Phase 2
18 Years
Open (Enrolling)
Non-small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

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Trial Information

Randomized Phase II Trial of Sequential Versus Concurrent Docetaxel and PS-341 (NSC 681239, IND 58,443) in Previously Treated Non-Small Cell Lung Cancer


I. To compare the efficacy and tolerability of sequential vs concurrent docetaxel and
bortezomib in patients with previously treated, progressive or recurrent, advanced non-small
cell lung cancer (NSCLC).


I. To compare time to progression in patients with previously treated NSCLC treated with
these regimens.

II. To compare 1-year and overall survival of patients treated with these regimens.

III. To compare the toxicity of these regimens in these patients. IV. To determine the
pharmacokinetics of docetaxel in the context of this study.


I. To determine levels of expression of molecular markers regulated by docetaxel and
bortezomib and correlate with clinical response and overall survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG
performance status (0 vs 1) and number of prior chemotherapy treatments (1 vs >1). Patients
are randomized to 1 of 2 treatment arms.

ARM I: Patients receive docetaxel IV over 60 minutes on day 1 and bortezomib IV over 3-5
seconds on days 1 and 8. Treatment repeats every 21 days for up to 8 courses in the absence
of disease progression or unacceptable toxicity.

ARM II: Patients receive docetaxel as in arm I and bortezomib IV over 3-5 seconds on days 2
and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically.

Inclusion Criteria


- No other prior malignancy except adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, adequately treated stage I or II cancer for which
the patient is currently in complete remission, or any other cancer for which the
patient has been disease-free for 5 years.

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).

- Progressive or recurrent NSCLC after treatment with 1 prior platinum-based
chemotherapy regimen for metastatic disease. Prior neoadjuvant/adjuvant chemotherapy
and/or concurrent chemoradiation for early-stage disease allowed.

- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
and recovered.

- No prior docetaxel or bortezomib

- Prior epidermal growth factor receptor inhibitor therapy allowed.

- Prior paclitaxel allowed

- At least 4 weeks since prior major surgery and recovered.

- At least 2 weeks since prior and no concurrent enzyme-inducing anticonvulsants.

- No concurrent hormonal therapy, biologic therapy, or radiotherapy to measurable
lesions. Concurrent palliative radiotherapy to small-field nonindicator lesions
(e.g., painful bony metastases) allowed.

- Measurable disease* with >= 1 unidimensionally objectively measurable lesion,
including any of the following:

- Lung mass (measurable on chest x-ray, tomograms, or CT scan)

- Enlarged lymph nodes

- Liver metastasis (measurable as a discrete focal lesion on radionuclide or CT scan,
or ultrasound)

- Metastatic abdominal mass (measurable on CT scan with >= 1 perpendicular diameter ≥
the distance between cuts)

- Measurable disease must be outside the previous radiation field or a new lesion must
be present.

- Life expectancy >= 12 weeks

- Progressive disease within a previously radiated field allowed.

- [Note: *Measurable disease DOES NOT include bone metastases or non-focal liver

- No symptomatic or untreated brain metastasis requiring steroids. Asymptomatic,
previously treated (surgical resection or radiotherapy) brain metastasis allowed
provided they are neurologically stable and >= 4 weeks since prior steroids.

- Creatinine clearance >= 50 mL/min

- Creatinine =< 1.6 mg/dL

- Bilirubin normal

- AST =< 2 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No peripheral neuropathy >= grade 2

- Absolute granulocyte count >= 1,500/mm³

- Platelet count >= 100,000/mm³

- Cutaneous nodule

- ECOG performance status 0-1

- At least 4 weeks since prior radiotherapy and recovered.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate for PS-341 and docetaxel given in two sequences and to decide whether this combination warrants further study

Outcome Description:

This objective corresponds to a one-sided test at the 0.5 level of significance, with 90% power.

Outcome Time Frame:

Up to 4 years

Safety Issue:


Principal Investigator

Primo Lara

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2006

Completion Date:

Related Keywords:

  • Non-Small Cell Lung Cancer
  • Recurrent Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



City of Hope Medical Center Duarte, California  91010