Evaluation of Safety and Feasibility of OGX-011 in Combination With 2nd-line Chemotherapy in Patients With HRPC

NCT00327340 | Completed Phase 2 Results

• 1 other identifier: OGX-011-07
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 10

Brief Summary

This study is for patients with cancer of the prostate gland that has metastasized or spread outside the prostate to other parts of the body. Patients have already been treated with a drug called docetaxel or Taxotere® (with or without the addition of a steroid called prednisone) some time in the recent past. They either did not respond to this therapy or responded to this therapy, but now the cancer is progressing (growing larger or has spread to other areas of the body). Custirsen (OGX-011) is an experimental drug that has been shown to increase the effectiveness of chemotherapy in several kinds of tumors, including prostate cancer. Both docetaxel and mitoxantrone have anticancer activity in prostate and are approved by Health Canada and the Food and Drug Administration for the treatment of patients with prostate cancer.

Conditions

Prostate Cancer

Keywords

Metastatic hormone refractory prostate cancer (HRPC)

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of Custirsen (OGX-011) in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second-line Chemotherapy.

  Safety and tolerability were based on Adverse Events (AE) and Serious Adverse Events (SAE) graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). The CTCAE has 5 grades with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1=Mild AE; Grade 2=Moderate AE; Grade 3=Severe AE; Grade 4=Life-threatening or disabling AE; and Grade 5=Death related to AE.

  Subjects were followed for safety from enrollment for up to 8 months (9 three-week cycles plus 30 days after end of treatment)

Secondary Outcomes (3)

• Feasibility of Treatment With Custirsen (OGX-011) in Combination With Second-line Chemotherapy Based on Prostate Specific Antigen (PSA) Response

  PSA was evaluated at screening, on Day 1 of each cycle, at the end of treatment visit and during off-treatment follow up (up to 27 months)

• Feasibility of Treatment With OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second Line Chemotherapy Based on Time to Pain Progression

  Enrollment until pain progression (up to 21 months)

• Relationship Between Changes in Serum Clusterin Levels and Change in Serum PSA Levels When OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone is Administered as Second Line Chemotherapy.

  Enrollment until disease progression (up to 13 months)

Study Arms (2)

OGX-011 / mitoxantrone/prednisone

EXPERIMENTAL

OGX-011 / mitoxantrone/prednisone: OGX-011 administered in combination with mitoxantrone and prednisone

Drug: custirsen (OGX-011)/mitoxantrone

OGX-011/docetaxel/prednisone

EXPERIMENTAL

OGX-011/docetaxel/prednisone: OGX-011 administered in combination with docetaxel and prednisone

Drug: custirsen (OGX-011)/docetaxel

Interventions

custirsen (OGX-011)/mitoxantrone DRUG

All subjects began treatment with oral prednisone (5 mg twice daily, 10 mg/day) continued through completion of the final treatment cycle. Three IV administrations of OGX-011 (640 mg) were given as 2 hr infusions during the loading dose period (Days-9 to-1). Subjects were premedicated with either ibuprofen (400 mg) or acetaminophen (650 mg) 30 to 60 minutes prior to and every 4-6 hours for 24 hours following each of the three doses of OGX-011 during the loading dose period only. After the loading dose period, OGX-011 was given weekly on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone was administered IV on Day 1 of each cycle at a planned dose of 12 mg/m² infused over 30 minutes. Patients could receive a maximum of 9 cycles of treatment.

Also known as: custirsen, OGX-011, TV-1011

OGX-011 / mitoxantrone/prednisone

custirsen (OGX-011)/docetaxel DRUG

All subjects began treatment with oral prednisone (5 mg twice daily, 10 mg/day) continued through completion of the final treatment cycle. Three IV administrations of OGX-011 (640 mg) were given as 2 hr infusions during the loading dose period (Days-9 to -1). Subjects were premedicated with either ibuprofen (400 mg) or acetaminophen (650 mg) 30 to 60 minutes prior to and every 4-6 hours for 24 hours following each of the three doses of OGX-011 during the loading dose period only. After the loading dose period, OGX-011 was given weekly on Days 1, 8, and 15 of each 21 day cycle. Docetaxel was administered IV on Day 1 of each cycle at a planned dose of 75 mg/m² infused over 60 minutes. Patients could receive a maximum of 9 cycles of treatment.

Also known as: custirsen, OGX-011, TV-1011

OGX-011/docetaxel/prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Histologic diagnosis of adenocarcinoma of the prostate.
• Metastatic disease on chest X-ray, bone scan, or computed tomography (CT) scan.
• Failed after receiving a minimum of two cycles of a docetaxel based first line therapy regimen. Failure is defined as disease progression within 6 months of discontinuing first line docetaxel therapy. Disease progression is defined as one or more of the following:
• Progressive measurable (target) disease (by Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria): at least a 20% increase in the sum of the longest diameters of measurable lesions (organ masses or lymph nodes) over the smallest sum observed (baseline or nadir) or the appearance of one or more new lesions as assessed by CT scan or chest X-ray.
• Bone scan progression: one or more new lesions on bone scan while on or following docetaxel treatment.
• Increasing serum PSA level: rise in PSA on three consecutive measurements obtained at least one week apart. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA will be acceptable.
• Baseline laboratory values as stated below:
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• Bilirubin ≤ 1.1 x ULN (unless elevated secondary to conditions such as Gilbert's disease)
• SGOT (AST) ≤ 1.5 x ULN
• Castrate serum testosterone level (\< 50 ng/mL-or-\< 1.7 mmol/L).
• If not treated with bilateral orchiectomy, patients must be willing to continue luteinizing hormone releasing hormone analogues throughout the study.
• Adequate bone marrow function defined as absolute neutrophil count (ANC) ≥ 1.5 x 10\^9 cells/L and platelet count ≥ 100 x 10\^9/L.
• Karnofsky score ≥ 60

You may not qualify if:

• Life expectancy less than 12 weeks.
• Patient is beyond 6 months following the last dose of docetaxel.
• Patient could not tolerate a dose of docetaxel of at least 45 mg/m² at the end of first line therapy due to toxicity.
• History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated. (Brain imaging in asymptomatic patients is not required.)
• Current symptomatic cord compression requiring surgery or radiation therapy. (Once treated, patients are eligible for the study.)
• Active second malignancy (except non melanomatous skin or superficial bladder cancer).
• Prior radiotherapy to \> 25% of the bone marrow.
• Uncontrolled medical conditions such as a major active infection, myocardial infarction or stroke within 3 months, uncontrolled hypertension, and/or significant concurrent medical illness, that, in the opinion of the Investigator, would preclude protocol therapy.
• History of or active congestive heart failure.
• Known allergy or hypersensitivity to docetaxel or polysorbate 80 (diluent).

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (10)

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

BC Cancer Agency

Vancouver, British Columbia, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Location

QEII Health Sciences

Halifax, Nova Scotia, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

London Regional Cancer Program

London, Ontario, Canada

Location

Toronto Sunnybrook

Toronto, Ontario, Canada

Location

Jewish General Hospital

Montreal, Quebec, Canada

Location

University of Montreal

Montreal, Quebec, Canada

Location

Related Publications (2)

• Saad F, Hotte S, North S, Eigl B, Chi K, Czaykowski P, Wood L, Pollak M, Berry S, Lattouf JB, Mukherjee SD, Gleave M, Winquist E; Canadian Uro-Oncology Group. Randomized phase II trial of Custirsen (OGX-011) in combination with docetaxel or mitoxantrone as second-line therapy in patients with metastatic castrate-resistant prostate cancer progressing after first-line docetaxel: CUOG trial P-06c. Clin Cancer Res. 2011 Sep 1;17(17):5765-73. doi: 10.1158/1078-0432.CCR-11-0859. Epub 2011 Jul 25.

  PMID: 21788353 RESULT

• Blumenstein B, Saad F, Hotte S, Chi KN, Eigl B, Gleave M, Jacobs C. Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration-resistant prostate cancer treated with custirsen. Cancer Med. 2013 Aug;2(4):468-77. doi: 10.1002/cam4.93. Epub 2013 May 28.

  PMID: 24156019 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

OGX-011

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Monica S. Krieger, PhD
• Organization: OncoGenex Pharmaceuticals

mkrieger@oncogenex.com

425-686-1558

Study Officials

• Fred Saad, MD, FRCS

  Université de Montréal

  PRINCIPAL INVESTIGATOR

• Eric Winquist, MD, MSc

  Western University, Canada

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2006
• First Posted: May 18, 2006
• Study Start: July 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: October 5, 2012
• Results First Posted: August 29, 2012

Record last verified: 2012-10

Locations

CA (10)