A Study of OGX-011/Gemcitabine/Platinum-Based Regimen in Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC)

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1-2 Study of Weekly OGX-011 Plus a Gemcitabine/Platinum-Based Regimen in Patients With Stage IIIB or IV Non Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00138658
• Other study ID #: OGX-011-05
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 26, 2005
• Last updated: February 2, 2012
• Start date: November 2004
• Est. completion date: March 2010

Study information

• Verified date: February 2012
• Source: OncoGenex Technologies
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

This clinical study will help determine if giving OGX-011 (custirsen sodium) in combination with gemcitabine (GEM) and cisplatin (CIS) or carboplatin (CARB) is a safe and effective treatment for patients with lung cancer. This study will help to assess the safety and anti-tumor effect of OGX-011 when given to patients in combination with GEM and CIS/CARB.

Description:

OGX-011 is an experimental drug that has been shown to increase the effectiveness of commonly used cancer therapies such as chemotherapy, radiation and hormone therapy in several kinds of cancer types in animals. OGX-011 is being studied in the treatment of cancer patients in combination with chemotherapy. In humans, OGX-011 in combination with hormone therapy has been shown to decrease the tissue levels of a protein called clusterin, which can be overproduced in cancer cells. Clusterin has been found to block cell death and makes cells more resistant to cancer therapy. Gemcitabine (GEM), cisplatin (CIS) and carboplatin (CARB) have been approved by Health Canada and the Food and Drug Administration in the United States for the treatment of patients with lung cancer.

OGX-011 was administered as a 2-hr intravenous (IV) infusion on Days -7, -5, and -3 prior to Cycle 1, then weekly on Days 1, 8, 15 of each 21-day cycle; GEM was infused IV after OGX-011 on Days 1 and 8; either CIS or CARB was infused IV after GEM on Day 1 of each cycle. Six cycles of treatment were planned. Most patients received OGX-011 at 640 mg, but 3 patients received OGX-011 at 480 mg dose; OGX-011 dose groups were combined due to the small number of patients who received 480 mg.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

1. Patients must have a histologically or cytologically confirmed diagnosis of NSCLC and must not have had chemotherapy or biological therapy for their disease.

2. Stage IIIB (N3 and/or pleural or pericardial effusion) or IV disease that is not amenable to either surgery or radiation therapy of curative intent.

3. Life expectancy of = 12 weeks

4. If patient has had prior radiation therapy: lesion(s) used for determination of response was not previously irradiated or has increased in size since the completion of radiotherapy; and patient has recovered from any toxicity from the radiotherapy.

5. Radiotherapy to lesion(s) used for determination of response was completed at least 6 weeks prior to treatment; radiotherapy to other sites was completed at least 2 weeks prior to treatment.

6. At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors [RECIST] (at least 10 mm in longest diameter by spiral computed tomography [CT] scan, or at least 20 mm by standard techniques).

7. ECOG status must be = 1

Exclusion Criteria

1. Prior chemotherapy or biological therapy (approved or experimental) for NSCLC, including adjuvant and neoadjuvant treatment.

2. Presence of central nervous system (CNS) metastases, unless the patient has completed successful local therapy for CNS metastases, with the exception of leptomeningeal disease for which patients will be excluded. Patients must be off corticosteroids for at least 21 days prior to starting treatment.

3. Second primary malignancy (except in situ carcinoma of the cervix, adequately treated non-melanomatous skin cancers, clinically localized prostate cancer, superficial bladder cancer or other malignancy treated at least 3 years previously with no evidence of recurrence).

4. Patients eligible for combined modality therapy with curative intent as defined by the combination of chemotherapy, radiation therapy and/or surgery. (This criteria is intended to exclude patients with stage IIIB disease, as defined by the presence of N3 nodal status, who have been reported to have cure rates as high as 10% when treated with combined modality therapy.)

Study Design

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• custirsen sodium
Custirsen sodium (OGX-011) was to be infused intravenously over 2 hours on Days -7, -5, and 3 of Cycle 1 (pretreatment loading dose). OGX 011 was then to be infused for 2 hours weekly on Days 1, 8, and 15 of a 21-day cycle. Gemcitabine (GEM) was to be infused intravenously for 30 minutes on Days 1 and 8 and either cisplatin (CIS) or carboplatin (CARBO) were to be infused intravenously on Day 1 of this 21-day cycle. Patients were to receive a maximum of 6 cycles (1 cycle = 21 days)

Locations

Country	Name	City	State
Canada	Royal Victoria Hospital of Barrie	Barrie	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	London Regional Cancer Centre	London	Ontario
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Dr. H. Bliss Murphy Cancer Center	St. Johns	Newfoundland and Labrador
Canada	Hopital Laval	Ste-Foy	Quebec
Canada	BC Cancer Agency, Fraser Valley Centre	Surrey	British Columbia
Canada	Toronto Sunnybrook Regional Cancer Center	Toronto	Ontario
Canada	BC Cancer Agency, Vancouver Center	Vancouver	British Columbia
United States	New York Oncology Hematology	Albany	New York
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	LAC-USC Medical Center	Los Angeles	California
United States	University of Southern California Norris	Los Angeles	California
United States	Oregon Health and Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
OncoGenex Technologies

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Laskin JJ, Nicholas G, Lee C, Gitlitz B, Vincent M, Cormier Y, Stephenson J, Ung Y, Sanborn R, Pressnail B, Nugent F, Nemunaitis J, Gleave ME, Murray N, Hao D. Phase I/II trial of custirsen (OGX-011), an inhibitor of clusterin, in combination with a gemci — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate of OGX-011 in Combination With Gemcitabine/Platinum-based Regimen	Per RECIST Criteria V 1.0 and based on radiographic evaluations a subject was defined as having an objective response (OR) if the subject achieved either a confirmed partial response (PR) or confirmed complete response (CR).; The evaluations were conducted after every two cycles of treatment for a maximum of 6 cycles.; CR: disappearance of clinical/radiological evidence of tumor.; PR: >= 30% decrease in the sum of the longest diameter of target lesions.; SD: did not fulfill the criteria for CR or PR but not progressive disease.	Based on assessments at baseline and after Cycles 2, 4, and 6. All subjects were followed for survival for a minimum of 3 years after the first dose of OGX-011 or until death.	No
Secondary	Progression-free Survival	Progression-free survival (PFS) was defined as time from first treatment with OGX-011 to documented evidence of disease progression or date of death. For subjects without disease progression based on RECIST who initiated subsequent anti-cancer therapy, date of progression was defined as date of initiating new cancer treatment. PFS was censored as of the date of first OGX-011 dose for subjects who failed to return for assessments after screening. For subjects who were still alive and without progressive disease at the time of data cut-off, PFS was censored at date of last disease assessment.	All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death.	No
Secondary	Overall Survival	Overall survival was defined as time from date of first treatment with OGX-011 to the date of death from any cause. Overall survival was censored at date of last contact for subjects who were still alive at end of study.	All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death.	No
Secondary	Effect of OGX-011 on Serum Clusterin Levels	To measure the effect of OGX-011 on serum clusterin levels. The drug substance, OGX-011, is an antisense product designed to bind to clusterin mRNA, resulting in the inhibition of the production of human clusterin protein. Therefore, serum clusterin levels were expected to decrease.	Blood samples were collected at baseline and prior to infusion on Cycle 2 Day 1 and Cycle 3 Day 1	No
Secondary	Cmax of OGX-011	Cmax is a plasma pharmacokinetic parameter that is defined as the maximum observed concentration of drug substance in plasma.	Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2.	No
Secondary	t1/2 of OGX-011	Plasma half life of OGX-011	Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2.	No
Secondary	AUC-0-last	AUC-0-last is the area under the plasma concentration time curve from time 0 to the last last time point (23.5 hrs)	Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2.	No