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

NCT ID: NCT00327340

Last Updated: 2012-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2010-10-31

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.

Detailed Description

This study was initiated as a multicenter, open-label, randomized study, with a planned enrollment of 40 subjects. Although two treatment arms were included in this study, no comparison between the arms was intended.

Subjects with metastatic HRPC who failed first-line docetaxel therapy and required second-line therapy were randomly assigned to treatment with OGX-011 in combination with docetaxel/prednisone (OGX-011/docetaxel/prednisone) or OGX-011 in combination with mitoxantrone/prednisone (OGX-011/mitoxantrone/ prednisone). The study was randomized to assure that subjects were enrolled in each of the two treatment arms in an unbiased manner.

Based on preliminary safety data from the first 44 subjects who were randomized to receive either docetaxel or mitoxantrone, the protocol was amended to enroll approximately 20 additional subjects who would be assigned to the docetaxel/prednisone treatment arm to further investigate safety of the combination.

Conditions

Prostate Cancer

Keywords

Metastatic hormone refractory prostate cancer (HRPC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OGX-011 / mitoxantrone/prednisone

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

Group Type: EXPERIMENTAL

custirsen (OGX-011)/mitoxantrone

Intervention Type: 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.

OGX-011/docetaxel/prednisone

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

Group Type: EXPERIMENTAL

custirsen (OGX-011)/docetaxel

Intervention Type: 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.

Interventions

custirsen (OGX-011)/mitoxantrone

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.

Intervention Type: DRUG

custirsen (OGX-011)/docetaxel

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.

Intervention Type: DRUG

Other Intervention Names

custirsen; OGX-011; TV-1011; custirsen; OGX-011; TV-1011

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Histologic diagnosis of adenocarcinoma of the prostate.

3. Metastatic disease on chest X-ray, bone scan, or computed tomography (CT) scan.

4. 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.

5. 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).

6. If not treated with bilateral orchiectomy, patients must be willing to continue luteinizing hormone releasing hormone analogues throughout the study.

7. 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.

8. Karnofsky score ≥ 60

9. Received no other chemotherapy, radioisotope therapy, strontium 89, or samarium 153. (Prior radiotherapy and steroids following first line docetaxel therapy are allowed.)

10. Received no more than one prior biological response modifier therapy following first line docetaxel therapy.

11. At least 21 days since completing the last dose of docetaxel, biological response modifier, and/or radiotherapy. (Exception for radiotherapy: at least 7 days since completing a single fraction of ≤ 800 cGy to a restricted field.)

12. Has recovered from all therapy related toxicity to ≤ grade 2, (except alopecia and anemia.)

13. Willing and able to give informed consent and follow protocol requirements.

Exclusion Criteria

1. Life expectancy less than 12 weeks.

2. Patient is beyond 6 months following the last dose of docetaxel.

3. Patient could not tolerate a dose of docetaxel of at least 45 mg/m² at the end of first line therapy due to toxicity.

4. History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated. (Brain imaging in asymptomatic patients is not required.)

5. Current symptomatic cord compression requiring surgery or radiation therapy. (Once treated, patients are eligible for the study.)

6. Active second malignancy (except non melanomatous skin or superficial bladder cancer).

7. Prior radiotherapy to > 25% of the bone marrow.

8. 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.

9. History of or active congestive heart failure.

10. Known allergy or hypersensitivity to docetaxel or polysorbate 80 (diluent).

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Achieve Life Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fred Saad, MD, FRCS

Role: PRINCIPAL_INVESTIGATOR

Université de Montréal

Eric Winquist, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Western University, Canada

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BC Cancer Agency

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

QEII Health Sciences

Halifax, Nova Scotia, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Toronto Sunnybrook

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

University of Montreal

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 21788353 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24156019 (View on PubMed)

Other Identifiers

OGX-011-07

Identifier Type: -

Identifier Source: org_study_id