- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00074022
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
A Phase I/2 Study of GTI-2040 Combined With Docetaxel In Metastatic Or Unresectable Locally Advanced Non-Small Cell Lung Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
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 regimen.
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Hospital Phase 2 Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 requirements
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (GTI-2040, docetaxel)
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 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 RP2D is defined as the dose preceding the MTD. Phase II: Patients receive GTI-2040 and docetaxel at the RP2D as in phase I. |
Correlative studies
Correlative studies
Other Names:
Given IV
Other Names:
Given IV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients experiencing dose limiting toxicities (DLTs), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 (Phase I)
Time Frame: Up to day 21
|
Up to day 21
|
|
Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II)
Time Frame: Up to day 42
|
The 95% confidence intervals will be provided.
|
Up to day 42
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to disease progression
Time Frame: Up to 4 years
|
Up to 4 years
|
|
Stable disease rate
Time Frame: Up to 6 weeks
|
Up to 6 weeks
|
|
Response duration
Time Frame: Up to 4 years
|
The 95% confidence intervals will be provided.
|
Up to 4 years
|
Toxicities of GTI-2040 combined with docetaxel, graded according to the NCI CTC v2.0
Time Frame: Up to 4 years
|
Up to 4 years
|
|
Duration of stable disease
Time Frame: Up to 6 weeks
|
Up to 6 weeks
|
|
Level of ribonucleotide reductase (RNR) activity
Time Frame: Up to week 10
|
Logistic regression and descriptive statistics will be used.
|
Up to week 10
|
Tumoral expression in terms of c-myc, R2 subunit protein levels and markers of proliferation (cyclin B1) and apoptosis (activated caspase 3)
Time Frame: Up to week 10
|
Logistic regression and descriptive statistics will be used.
|
Up to week 10
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Natasha Leighl, Princess Margaret Hospital Phase 2 Consortium
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Disease Attributes
- Genital Neoplasms, Male
- Prostatic Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Prostatic Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Recurrence
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Docetaxel
Other Study ID Numbers
- NCI-2012-02563
- N01CM17107 (U.S. NIH Grant/Contract)
- PMH-PHL-017
- CDR0000341677 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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