AzTrials
AzTrials

Castration Resistant Prostate CancerPhase 2NCT01120470

OGX-427 in Castration Resistant Prostate Cancer Patients

A Phase 2 study testing OGX-427 and Prednisone in people with Castration Resistant Prostate Cancer, run by British Columbia Cancer Agency at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Castration Resistant Prostate Cancer
What is being tested?
OGX-427 and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
74 participants
Where
6 sitesin 2 countries
Study dates
Sep 2010to Jun 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 25Show fewer
  • 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.
  • Baseline laboratory values as stated below:
  • ANC ≥ 1.5 x 109 cells /L, platelet count ≥ .100 x 109 /L, and hemoglobin ≥ 9 g/dL without transfusion.
  • Creatinine ≤ 1.5 x upper limit of normal (ULN).
  • Total bilirubin ≤ 1.1 x ULN (unless elevated secondary to conditions such as Gilbert's disease).
  • SGPT (ALT) and SGOT (AST) ≤ 2.5 x ULN.
  • Castrate serum testosterone level (< 50 ng/dL-or-< 1.7 nmol/L).
  • Recovery from all toxicities of prior therapy to ≤ grade 2 by NCI CTCAE, version 3.0. (Exception: any toxicity that in the view of the Investigator is not a clinically significant safety risk for further therapy administration, including, but not limited to: anemia, fatigue, erectile dysfunction, hot flashes, lymphedema of an extremity, dizziness, cough, and urinary incontinence).
  • Must be willing to use effective contraception, if of child bearing potential, throughout study treatment and for 3 months after completion of study treatment.
  • Must be willing not to change (add or subtract) bone protecting therapy (bisphosphonates and/or denosumab) during the study unless changed for toxicity.
  • Written informed consent must be obtained prior to any protocol-specific procedures being performed.

Who cannot join

  • 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).
Show all 9Show fewer
  • 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.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

Canada5 sites

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • BC Cancer Agency - Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • BC Cancer Agency - Vancouver Centre

    Vancouver, British Columbia, V5Z 4E6

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

United States1 site

  • University of Washington/Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Randomized Phase II Study of OGX-427 (a Second-Generation Antisense Oligonucleotide to Heat Shock Protein-27) in Patients With Castration Resistant Prostate Cancer Who Have Not Previously Received Chemotherapy for Metastatic Disease

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%.

Read the detailed description

Prostate cancer is the most common cancer diagnosed and the second most common cause of cancer death in men in North America.

Patients with metastatic disease have a poor prognosis, and although hormonal therapy in the form of medical or surgical castration can induce significant long-term remissions, development of androgen independent disease is inevitable. The current standard of care for CRPC is mainly palliative in its intent, and there are only limited proven treatment options which include: analgesia, radiation, bisphosphonates and chemotherapy such as mitoxantrone or docetaxel, with only the last treatment being associated with an overall survival benefit.

With the early commencement of androgen deprivation therapy and frequent use of PSA for monitoring disease progression, an increasing population of patients with CRPC is now being identified by a rising PSA rather than by new disease or symptoms. Early intervention with chemotherapy is of unknown benefit in these patients, and thus represents an appropriate group for phase II studies to evaluate novel agents with acceptable toxicity profiles.

Heat shock protein (Hsp) family members, including Hsp27, have attracted attention as new therapeutic targets for cancer. Hsp27 is a small, ATP-independent Hsp which is highly conserved across species. Hsp27 is expressed in prostate cancer and other malignancies. Expression of Hsp27 is induced by cell stress, including cytotoxic chemotherapy, radiation therapy, and hormone therapy. Overexpression of Hsp27 confers a resistant phenotype and is implicated in castration resistant progression of prostate cancer.

OGX 427 is a second generation antisense oligonucleotide (ASO) that inhibits expression of Hsp27. A number of in vitro and in vivo pharmacological studies have demonstrated that OGX 427 (or an Hsp27 ASO) has single-agent activity in reducing Hsp27 mRNA and protein, inhibiting cell proliferation, and inducing apoptosis in several human cancer cell lines. OGX 427 has also demonstrated chemosensitizing activity both in vitro and in vivo in combination with several cytotoxic drugs, including docetaxel. In an ongoing Phase I trial, OGX-427 has been administered as a single agent in doses from 200 to 1000 mg with weekly infusions occurring after a loading dose period of three infusions within the first 10 days of initiating treatment. OGX-427 treatment has been well tolerated, with the majority of the adverse events and laboratory toxicities reported being Grade 1 or Grade 2, although a symptom complex of rigors, pruritus, and erythema during or shortly after infusion of drug has required steroid prophylaxis and/or treatment in some patients at higher doses. No maximum tolerated dose has been identified based on toxicity. OGX 427 administration in combination with docetaxel is ongoing in the above-mentioned Phase 1 study.

Low dose corticosteroids have been shown to have some activity against prostate cancer with a beneficial effect on quality of life (QOL). Since chemotherapy for prostate cancer is palliative, low-dose prednisone has been used both as a single agent and added to chemotherapy regimens.

This Phase 2 study has been designed to evaluate the anti-tumor effects of OGX-427 plus low-dose prednisone versus low-dose prednisone alone in men with CRPC who have not previously received chemotherapy for metastatic or locally recurrent disease.

Being tested
OGX-427, Prednisone
Keywords
Castration Resistant, Prostate Cancer, OGX-427
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OGX-427Drug

    Also called Apatorsen

    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

  • PrednisoneDrug

    Also called Rayos, Sterapred

    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

Study groups in NCT01120470
Study groupRoleWhat they receive
OGX-427 and PrednisoneExperimentalOGX-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
Receives: Drug: OGX-427; Drug: Prednisone
PrednisoneActive comparatorControl Arm: Prednisone: 5 mg BID orally starting within 4 days following randomization
Receives: Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2010 (estimated)
  2. Study startSep 2010
  3. Primary completionOct 2012
  4. Study completionJun 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
74 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01120470
Sponsor's protocol ID
PR-01
Status last verified
Feb 2019
First submitted
7 May 2010
Last updated
15 Feb 2019
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 18309951

  • 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.

    PubMed 22894553

  • 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.

    PubMed 21612468

  • 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.

    PubMed 23228172

  • 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.

    PubMed 26685010

  • 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.

    PubMed 20888992

  • 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.

    PubMed 16682719

  • 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.

    PubMed 10550143

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing OGX-427 and Prednisone in people with Castration Resistant Prostate Cancer, run by British Columbia Cancer Agency at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Progression (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01120470, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in