OGX-427 in Castration Resistant Prostate Cancer Patients

NCT01120470 | Completed Phase 2

• 1 other identifier: PR-01
• Study Type: interventional
• Target: 74
• Locations: 2 countries
• Sites: 6

Brief Summary

This study is being offered to patients who have castrate-resistant (also known as hormone-refractory) prostate cancer. The cancer has metastasized or spread outside the prostate area to other parts of the body or has recurred in the pelvic area after treatment. The purpose of this clinical research study is to determine whether OGX-427 is able to slow the progression of prostate cancer and symptoms of disease when given with prednisone better than when prednisone is given alone in patients with prostate cancer whose disease has spread outside the prostate area. Research Hypothesis: That adding OGX-427 to prednisone treatment will produce a progression free rate of 20%.

Conditions

Castration Resistant Prostate Cancer

Keywords

Castration Resistant; Prostate Cancer; OGX-427

Outcome Measures

Primary Outcomes (1)

• Disease Progression

  The primary efficacy endpoint is defined as the proportion of patients without disease progression at the 12-week evaluation after treatment with prednisone given with or without OGX-427.

  12 weeks

Study Arms (2)

OGX-427 and Prednisone

EXPERIMENTAL

OGX-427: Starting within 5 days of randomization, three loading doses at 600 mg IV within the first 10 days of initiating treatment, followed by weekly doses of 1000 mg IV Prednisone: 5 mg BID orally starting within 4 days following randomization and at least 24 hours prior to first loading dose of OGX-427

Drug: OGX-427; Drug: Prednisone

Prednisone

ACTIVE COMPARATOR

Control Arm: Prednisone: 5 mg BID orally starting within 4 days following randomization

Drug: Prednisone

Interventions

OGX-427 DRUG

OGX-427: Starting within 5 days of randomization, three loading doses at 600 mg IV within the first 10 days of initiating treatment, followed by weekly doses of 1000 mg IV

Also known as: Apatorsen

OGX-427 and Prednisone

Prednisone DRUG

Control Arm: Prednisone: 5 mg BID orally starting within 4 days following randomization Experimental Arm: Prednisone: 5 mg BID orally starting within 4 days following randomization and at least 24 hours prior to first loading dose of OGX-427

Also known as: Rayos, Sterapred

OGX-427 and Prednisone; 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 on the date of consent.
• ECOG performance status of 0 or 1.
• Histological or cytological diagnosis of adenocarcinoma of the prostate.
• Metastatic disease on chest, abdominal, or pelvic CT and/or bone scan for which no curative therapy exists.
• Progression of prostate cancer. Progression is defined by one or more of the following:
• Increasing serum PSA level: two consecutive increases in PSA levels documented over a previous reference value 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 is acceptable. The last confirmation PSA value must be obtained within the 14 days prior to randomization. A minimum starting value of 2.0 ng/mL is required for study randomization.
• Progressive measurable disease: at least a 20% increase in the sum of the diameters of measurable lesions over the smallest sum observed or the appearance of one or more new lesions as assessed by CT scan. Measurable lesions are nodal or visceral soft-tissue lesions with nodal lesions ≥ 15 mm in diameter at the shortest axis and visceral/soft-tissue lesions ≥ 10 mm in longest diameter (See Section 6.4).
• Bone Progression: appearance of 2 or more new lesions on bone scan (or other imaging).
• All patients who have not had a surgical orchiectomy must continue treatment with LHRH agonist or antagonist to maintain a castrate level of testosterone.
• Patient must fulfill "Prior Therapy" criteria as follows:
• Chemotherapy: No prior chemotherapy for metastatic disease is permissible. (Exception: neoadjuvant/adjuvant chemotherapy if received \> 12 months prior to randomization.)
• Hormone therapy: prior surgical or medical castration therapy is required. Prior treatment with non-steroidal antiandrogens, abiraterone or other experimental hormone therapy (e.g. MDV3100, YAK-700) is allowed provided a minimum of at least 14 days have passed since completing therapy and randomization in the study.
• Experimental therapy: prior non-cytotoxic experimental therapy is permitted provided a minimum of at least 14 days has passed since completing therapy prior to randomization.
• Radiation: prior external beam radiation is permitted provided a minimum of at least 28 days have passed since completing radiotherapy at the time of randomization (or following disease progression and prior to receiving therapy at the time of cross-over). Exception for radiotherapy: at least 7 days must have passed since completing single fraction of ≤ 800 cGy.
• Corticosteroids: prior corticosteroid therapy is permitted. Within 4 days following randomization, all patients must be taking prednisone 5 mg BID.

You may not qualify if:

• Unable to tolerate a dose of 10 mg of prednisone a day.
• Requiring an amount of opioids to control pain \> 30 mg of a morphine-equivalent per day.
• Known coagulopathy or actively receiving warfarin (Coumadin) therapy.
• Documented brain metastases, or carcinomatous meningitis, treated or untreated (Brain imaging for asymptomatic patients is not required).
• Current symptomatic cord compression requiring surgery or radiation therapy (once successfully treated and there has been no progression, patients are eligible for the study).
• Active second malignancy (except adequately treated non-melanomatous skin cancer or other solid tumors curatively treated with no evidence of disease \> 3 years).
• History of allergic reactions to therapeutic antisense oligonucleotides.
• Uncontrolled medical conditions such as heart failure, myocardial infarction, uncontrolled hypertension, stroke or treatment of a major active infection within 3 months of randomization, as well as any significant concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy.
• Planned concomitant participation in another clinical trial of an experimental agent, vaccine, or device. Concomitant participation in observational studies is acceptable.

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• Achieve Life Sciences: collaborator

Study Sites (6)

University of Washington/Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

BC Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BC Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (8)

• Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. doi: 10.1200/JCO.2007.12.4487.

  PMID: 18309951 BACKGROUND

• Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. doi: 10.1056/NEJMoa1207506. Epub 2012 Aug 15.

  PMID: 22894553 BACKGROUND

• de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. doi: 10.1056/NEJMoa1014618.

  PMID: 21612468 BACKGROUND

• Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. doi: 10.1056/NEJMoa1209096. Epub 2012 Dec 10.

  PMID: 23228172 BACKGROUND

• Chi KN, Kheoh T, Ryan CJ, Molina A, Bellmunt J, Vogelzang NJ, Rathkopf DE, Fizazi K, Kantoff PW, Li J, Azad AA, Eigl BJ, Heng DY, Joshua AM, de Bono JS, Scher HI. A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel. Ann Oncol. 2016 Mar;27(3):454-60. doi: 10.1093/annonc/mdv594. Epub 2015 Dec 18.

  PMID: 26685010 BACKGROUND

• de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. doi: 10.1016/S0140-6736(10)61389-X.

  PMID: 20888992 BACKGROUND

• Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006 Jul 1;24(19):3187-205. doi: 10.1200/JCO.2006.06.4451. Epub 2006 May 8.

  PMID: 16682719 BACKGROUND

• Bubley GJ, Carducci M, Dahut W, Dawson N, Daliani D, Eisenberger M, Figg WD, Freidlin B, Halabi S, Hudes G, Hussain M, Kaplan R, Myers C, Oh W, Petrylak DP, Reed E, Roth B, Sartor O, Scher H, Simons J, Sinibaldi V, Small EJ, Smith MR, Trump DL, Wilding G, et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 1999 Nov;17(11):3461-7. doi: 10.1200/JCO.1999.17.11.3461.

  PMID: 10550143 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apatorsen; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Kim N Chi, MD

  BC Cancer Agency - Vancouver Center

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: May 7, 2010
• First Posted: May 11, 2010
• Study Start: September 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: June 1, 2014
• Last Updated: February 15, 2019

Record last verified: 2019-02

Locations

CA (5); US (1)