Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00074022
Other study ID # NCI-2012-02563
Secondary ID PMH-PHL-017N01CM
Status Completed
Phase Phase 1/Phase 2
First received December 10, 2003
Last updated January 23, 2013
Start date October 2003

Study information

Verified date January 2013
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

Phase I/II trial to study the effectiveness of combining GTI-2040 with docetaxel in treating patients who have recurrent, metastatic, or unresectable locally advanced non-small cell lung cancer, prostate cancer, or other solid tumors. GTI-2040 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of docetaxel by making the tumor cells more sensitive to the drug. Combining GTI-2040 with docetaxel may kill more tumor cells


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.


Recruitment information / eligibility

Status Completed
Enrollment 48
Est. completion date
Est. primary completion date November 2007
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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 Design

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


Related Conditions & MeSH terms


Intervention

Biological:
GTI-2040
Given IV
Drug:
docetaxel
Given IV
Other:
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies

Locations

Country Name City State
Canada Princess Margaret Hospital Phase 2 Consortium Toronto Ontario

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of patients experiencing dose limiting toxicities (DLTs), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 (Phase I) Up to day 21 Yes
Primary Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II) The 95% confidence intervals will be provided. Up to day 42 No
Secondary Stable disease rate Up to 6 weeks No
Secondary Response duration The 95% confidence intervals will be provided. Up to 4 years No
Secondary Toxicities of GTI-2040 combined with docetaxel, graded according to the NCI CTC v2.0 Up to 4 years Yes
Secondary Time to disease progression Up to 4 years No
Secondary Duration of stable disease Up to 6 weeks No
Secondary Level of ribonucleotide reductase (RNR) activity Logistic regression and descriptive statistics will be used. Up to week 10 No
Secondary Tumoral expression in terms of c-myc, R2 subunit protein levels and markers of proliferation (cyclin B1) and apoptosis (activated caspase 3) Logistic regression and descriptive statistics will be used. Up to week 10 No
See also
  Status Clinical Trial Phase
Completed NCT01828775 - Palliative Care Intervention in Improving Quality of Life, Psychological Distress, and Communication in Patients With Solid Tumors Receiving Treatment N/A
Terminated NCT01642342 - Recombinant Albumin Fusion Protein sEphB4-HSA in Treating Patients With Metastatic or Recurrent Solid Tumors Phase 1
Completed NCT00002950 - Topotecan Plus Sargramostim in Treating Patients With Advanced Cancer Phase 1/Phase 2
Completed NCT01705548 - Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis N/A
Completed NCT02146222 - VEGFR/PDGFR Dual Kinase Inhibitor X-82 and Docetaxel in Treating Patients With Solid Tumors Phase 1
Terminated NCT01602627 - Hsp90 Inhibitor AUY922 in Treating Older Patients With Advanced Solid Malignancies Phase 1
Completed NCT01191216 - 1-Methyl-D-Tryptophan and Docetaxel in Treating Patients With Metastatic Solid Tumors Phase 1
Recruiting NCT01137825 - Registry of Older Patients With Cancer
Recruiting NCT00992303 - Collecting Tissue Samples From Patients With Cancer Undergoing Radiation Therapy and Healthy Participants
Suspended NCT00935090 - 3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer N/A
Completed NCT00949949 - Everolimus, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable Solid Tumors Refractory to Standard Therapy Phase 1
Completed NCT00924651 - Exercise in Lessening Fatigue Caused by Cancer in Patients Undergoing Chemotherapy Phase 3
Withdrawn NCT00937417 - S0716 Vandetanib and Docetaxel in Treating Patients With Advanced Solid Tumors Phase 1
Active, not recruiting NCT00710632 - Screening to Predict Weight Loss in Patients With Cancer N/A
Completed NCT00573690 - Sorafenib Combined With Cisplatin and Etoposide or Carboplatin and Pemetrexed in Treating Patients With Metastatic Solid Tumors Phase 1
Completed NCT00544596 - R-(-)-Gossypol Acetic Acid, Cisplatin, and Etoposide in Treating Patients With Advanced Solid Tumors or Extensive Stage Small Cell Lung Cancer Phase 1
Active, not recruiting NCT00436735 - Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors Phase 1
Completed NCT00352443 - S0528 Lapatinib and Everolimus in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma Phase 1
Completed NCT00255658 - Sorafenib and Temsirolimus in Treating Patients With Unresectable or Metastatic Solid Tumors Phase 1
Completed NCT00126620 - Sorafenib and Erlotinib in Treating Patients With Metastatic or Unresectable Solid Tumors Phase 1