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

• ClinicalTrials.gov Identifier: NCT00138658
• Recruitment Status: Completed
• First Posted: August 30, 2005
• Results First Posted: January 10, 2012
• Last Update Posted: February 6, 2012
• Sponsor: Achieve Life Sciences
• Information provided by (Responsible Party): Achieve Life Sciences

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: custirsen sodium	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: November 2004
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

Intervention Details:

• 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)
  Other Names:

  • OGX-011
  • TV-1011

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate of OGX-011 in Combination With Gemcitabine/Platinum-based Regimen [ Time Frame: 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. ]

   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.

Secondary Outcome Measures :

1. Progression-free Survival [ Time Frame: All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death. ]
   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.
2. Overall Survival [ Time Frame: All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death. ]
   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.
3. Effect of OGX-011 on Serum Clusterin Levels [ Time Frame: Blood samples were collected at baseline and prior to infusion on Cycle 2 Day 1 and Cycle 3 Day 1 ]
   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.
4. Cmax of OGX-011 [ Time Frame: 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. ]
   Cmax is a plasma pharmacokinetic parameter that is defined as the maximum observed concentration of drug substance in plasma.
5. t1/2 of OGX-011 [ Time Frame: 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. ]
   Plasma half life of OGX-011
6. AUC-0-last [ Time Frame: 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. ]
   AUC-0-last is the area under the plasma concentration time curve from time 0 to the last last time point (23.5 hrs)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.)

Contacts and Locations

Locations

United States, California

LAC-USC Medical Center

Los Angeles, California, United States, 90033

University of Southern California Norris

Los Angeles, California, United States, 90033

United States, New York

New York Oncology Hematology

Albany, New York, United States, 12208

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, South Carolina

Cancer Centers of the Carolinas

Greenville, South Carolina, United States, 29605

United States, Texas

Mary Crowley Medical Research Center

Dallas, Texas, United States, 75246

Canada, Alberta

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Canada, British Columbia

BC Cancer Agency, Fraser Valley Centre

Surrey, British Columbia, Canada

BC Cancer Agency, Vancouver Center

Vancouver, British Columbia, Canada

Canada, Newfoundland and Labrador

Dr. H. Bliss Murphy Cancer Center

St. Johns, Newfoundland and Labrador, Canada

Canada, Ontario

Royal Victoria Hospital of Barrie

Barrie, Ontario, Canada

London Regional Cancer Centre

London, Ontario, Canada

Ottawa Hospital

Ottawa, Ontario, Canada

Toronto Sunnybrook Regional Cancer Center

Toronto, Ontario, Canada

Canada, Quebec

Hopital Laval

Ste-Foy, Quebec, Canada

Sponsors and Collaborators

Achieve Life Sciences

Investigators

• Principal Investigator: Janessa Laskin, M.D.; BCCA, Vancouver Clinic

More Information

Publications of Results:

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.

• Responsible Party: Achieve Life Sciences
• ClinicalTrials.gov Identifier: NCT00138658
• Other Study ID Numbers: OGX-011-05
• First Posted: August 30, 2005
• Results First Posted: January 10, 2012
• Last Update Posted: February 6, 2012
• Last Verified: February 2012

Keywords provided by Achieve Life Sciences:

NSCLC; custirsen sodium; OGX-011; Stage IIIB or IV advanced non-small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms