Clinical trial NCT00138658: A Study of OGX-011/Gemcitabine/Platinum-Based Regimen in Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: NSCLC
custirsen sodium
OGX-011
Stage IIIB or IV advanced non-small cell lung cancer
Lead sponsor: Achieve Life Sciences
Sponsor class: INDUSTRY
First posted: 2005-08-30
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.)

Primary outcomes:
measure: Objective Response Rate of OGX-011 in Combination With Gemcitabine/Platinum-based Regimen
timeFrame: 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.
Secondary outcomes:
measure: Progression-free Survival
timeFrame: All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death.
measure: Overall Survival
timeFrame: All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death.
measure: Effect of OGX-011 on Serum Clusterin Levels
timeFrame: Blood samples were collected at baseline and prior to infusion on Cycle 2 Day 1 and Cycle 3 Day 1
measure: Cmax of OGX-011
timeFrame: 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.
measure: t1/2 of OGX-011
timeFrame: 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.
measure: AUC-0-last
timeFrame: 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.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: LAC-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California Norris
state: California
city: Albany
country: United States
facility: New York Oncology Hematology
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Surrey
country: Canada
facility: BC Cancer Agency, Fraser Valley Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BC Cancer Agency, Vancouver Center
state: British Columbia
city: St. Johns
country: Canada
facility: Dr. H. Bliss Murphy Cancer Center
state: Newfoundland and Labrador
city: Barrie
country: Canada
facility: Royal Victoria Hospital of Barrie
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Center
state: Ontario
city: Ste-Foy
country: Canada
facility: Hopital Laval
state: Quebec
Study officials:
affiliation: BCCA, Vancouver Clinic
name: Janessa Laskin, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 gemcitabine and platinum regimen in patients with previously untreated advanced non-small cell lung cancer. J Thorac Oncol. 2012 Mar;7(3):579-86. doi: 10.1097/JTO.0b013e31823f459c.