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A Phase I/2 Study of GTI-2040 Combined With Docetaxel In Metastatic Or Unresectable Locally Advanced Non-Small Cell Lung Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Recurrent Non-small Cell Lung Cancer, Recurrent Prostate Cancer, Stage III Prostate Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer, Stage IV Prostate Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I/2 Study of GTI-2040 Combined With Docetaxel In Metastatic Or Unresectable Locally Advanced Non-Small Cell Lung Cancer


I. Determine the recommended phase II dose of GTI-2040 and docetaxel in patients with
recurrent, metastatic, or unresectable locally advanced non-small cell lung cancer, prostate
cancer, or other solid tumors (phase I study closed to accrual as of 8/5/2004).

II. Determine the toxicity of this regimen in these patients. III. Determine the objective
tumor response rate in patients treated with this regimen.

IV. Determine the stable disease rate, time to disease progression, objective response
duration, and duration of stable disease in patients treated with this regimen.

V. Determine the pharmacokinetics of GTI-2040 when administered in combination with
docetaxel in these patients.

VI. Correlate the pharmacokinetics of GTI-2040 with the biological and toxic effects of this
regimen in these patients.

VII. Correlate baseline and post-treatment levels of ribonucleotide reductase activity in
tumor biopsies and peripheral blood mononuclear cells and tumoral expression of c-myc, ras,
pRAF1, pMAPK, and markers of apoptosis with clinical outcome in patients treated with this

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Phase I (closed to accrual as of 8/5/2004): Patients receive GTI-2040 IV continuously on
days 1-14. Patients also receive docetaxel IV over 1 hour on day 3 during course 1 and on
day 1 for all subsequent courses. Courses repeat every 21 days in the absence of disease
progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of GTI-2040 and docetaxel until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. The recommended phase II dose (RP2D) is defined
as the dose preceding the MTD.

Phase II: Patients receive GTI-2040 and docetaxel at the RP2D as in phase I.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 12-48 patients (12-18 for phase I [closed to accrual as of
8/5/2004] and 15-30 for phase II) will be accrued for this study within 4-16 months.

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of 1 of the following:

- Solid tumor malignancy (phase I only)*

- Prostate cancer (phase I only)*

- Non-small cell lung cancer (phase I and II)*

- Recurrent, metastatic, locally advanced unresectable, or treatment-refractory disease

- Measurable disease

- At least 1 unidimensionally measurable lesion at least 20 mm by conventional
techniques OR at least 10 mm by spiral CT scan

- Previously irradiated lesions are considered measurable provided they have
demonstrated progression before study entry

- No bone-only disease

- Must have measurable disease other than bone lesions

- No stage IIIA or IIIB non-small cell lung cancer without a malignant pleural or
pericardial effusion that is eligible for first-line radical combined chemotherapy
and radiotherapy

- No known progressive or symptomatic brain metastases

- Asymptomatic brain metastases allowed

- Performance status - ECOG 0-2

- Performance status - Karnofsky 60-100%

- More than 3 months

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No history of coagulopathy

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- AST/ALT no greater than 2 times ULN (3.5 times ULN if liver metastases are present)

- INR no greater than 1.3

- APTT no greater than 1.25 times ULN

- Creatinine no greater than 1.5 times ULN

- Creatinine clearance at least 50 mL/min

- No symptomatic congestive heart failure

- No evidence of cardiac dysfunction

- No unstable angina pectoris

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active peptic ulcer disease

- No poorly controlled diabetes mellitus

- No pre-existing grade 2 or greater neuropathy

- No ongoing or active infection

- No contraindication to corticosteroids

- No psychiatric illness or social situation that would limit compliance with study

- No prior allergic reaction attributed to compounds of similar chemical or biological
composition to study drugs

- No other concurrent uncontrolled illness

- One, and only one, prior chemotherapy regimen for advanced disease (not including
adjuvant therapy) allowed

- Neoadjuvant/adjuvant chemotherapy allowed

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
and recovered

- Prior multiple lines of endocrine therapy for advanced solid tumors allowed

- More than 4 weeks since prior endocrine therapy and recovered

- Concurrent steroids allowed

- See Disease Characteristics

- More than 4 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy to sole site of measurable disease

- Prior surgery allowed

- No concurrent anticoagulant therapy

- Concurrent low-dose warfarin for central line thrombosis prophylaxis allowed

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational or commercial agents or therapies intended to
treat the malignancy

- Concurrent bisphosphonates allowed

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of patients experiencing dose limiting toxicities (DLTs), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 (Phase I)

Outcome Time Frame:

Up to day 21

Safety Issue:


Principal Investigator

Natasha Leighl

Investigator Role:

Principal Investigator

Investigator Affiliation:

Princess Margaret Hospital Phase 2 Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

October 2003

Completion Date:

Related Keywords:

  • Recurrent Non-Small Cell Lung Cancer
  • Recurrent Prostate Cancer
  • Stage III Prostate Cancer
  • Stage IIIA Non-Small Cell Lung Cancer
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Stage IV Prostate Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Prostatic Neoplasms