Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	NCI	PMH-PHL-017 NCI-6104, NCT00074022, 6104

Objectives

1. 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).
2. Determine the toxicity of this regimen in these patients.
3. Determine the objective tumor response rate in patients treated with this regimen.
4. Determine the stable disease rate, time to disease progression, objective response duration, and duration of stable disease in patients treated with this regimen.
5. Determine the pharmacokinetics of GTI-2040 when administered in combination with docetaxel in these patients.
6. Correlate the pharmacokinetics of GTI-2040 with the biological and toxic effects of this regimen in these patients.
7. 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 regimen.

Entry Criteria

Disease Characteristics:

• 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)*

   [Note: *Phase I study closed to accrual as of 8/5/2004]

• 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

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• 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

Endocrine therapy

• Prior multiple lines of endocrine therapy for advanced solid tumors allowed
• More than 4 weeks since prior endocrine therapy and recovered
• Concurrent steroids allowed

Radiotherapy

• See Disease Characteristics
• More than 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy to sole site of measurable disease

Surgery

• Prior surgery allowed

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• No history of coagulopathy

Hepatic

• 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

Renal

• Creatinine no greater than 1.5 times ULN

  OR

• Creatinine clearance at least 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No evidence of cardiac dysfunction
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• 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 requirements
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs
• No other concurrent uncontrolled illness

Expected Enrollment

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.

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.

Trial Contact Information

Trial Lead Organizations

Princess Margaret Hospital

Natasha Leighl, MD, FRCPC, Protocol chair		Ph: 416-946-2399

Registry Information
Official Title		A Phase I/2 Study of GTI-2040 Combined With Docetaxel In Metastatic Or Unresectable Locally Advanced Non-Small Cell Lung Cancer
Trial Start Date		2003-11-28
Registered in ClinicalTrials.gov		NCT00074022 1
Date Submitted to PDQ		2003-10-22
Information Last Verified		2006-09-25
NCI Grant/Contract Number		CM17107

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00074022