Safety Study of an Antisense Product in Prostate, Ovarian, NSCL, Breast or Bladder Cancer

NCT00487786 | Completed Phase 1 DMC

• 1 other identifier: OGX-427-01
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 3

Brief Summary

This study is for patients with cancer who have failed potentially curative treatments or for whose disease a curative treatment does not exist. OGX-427 is an antisense product that inhibits expression of one of the heat shock proteins. Decreasing this heat shock protein (Hsp27) should result in down regulation of pathways implicated in cancer progression and development of resistance to treatment.

Conditions

Neoplasms

Keywords

Antisense; Heat Shock Protein

Outcome Measures

Primary Outcomes (2)

• • To determine the maximum tolerated dose (MTD) of OGX-427 when administered as a single agent, up to a 1000 mg dose level.

  approximately 2 years

• • To further evaluate the safety profile at one dose level below the MTD derived for OGX-427 administered as a single agent and at the MTD level when OGX 427 is administered in combination with a taxane chemotherapy (docetaxel).

  approximately 2 years

Secondary Outcomes (6)

• To determine the pharmacokinetic profile of OGX-427 when used as a single agent and when used in combination with a taxane.

  approximately 2 years

• To determine whether OGX-427 alone or when co-administered with a taxane alters ECG intervals and morphology.

  approximately 2 years

• To document objective responses and disease stabilization when OGX-427 is administered either alone or in combination with a taxane.

  approximately 2 years

• To assess for a biologically effective dose(s) of OGX-427 that inhibits Hsp27 and other related protein levels in patient's serum.

  approximately 2 years

• To assess for a biologically effective dose(s) of OGX-427 when used as a single agent that reduces serum PSA levels in patients with HRPC.

  approximately 2 years

Study Arms (1)

A

EXPERIMENTAL

Each patient receives OGX-427

Drug: OGX-427; Drug: Docetaxel

Interventions

OGX-427 DRUG

OGX-427 injection at 200mg, 400mg, 600mg, 800mg or 1000mg once a week until withdrawn

A

Docetaxel DRUG

injection - 75 mg/M2 IV on Day 1 every 21 days for cohorts 6 \& 7 only, together with appropriate dose of OGX-427 until withdrawn from study

Also known as: Taxotere

A

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at time of consent.
• Histologically or cytologically confirmed diagnosis of one of the following: adenocarcinoma of the breast, ovary, or prostate, any NSCLC or bladder cancer.
• Must have metastatic disease. Prostate cancer patients must be hormone refractory.
• Must have failed therapies that are potentially curative; failed/refused standard therapy known to prolong survival or progression-free survival; or failed/refused therapy, that in the view of the investigator, would be beneficial in improvement of symptoms
• Patients enrolled into Cohorts 6 and 7 (OGX 427 in combination with docetaxel) must have disease that has a possibility of responding to docetaxel.
• A minimum of 28 days must have elapsed between any major surgery, the last dose of chemotherapy, radiotherapy (except limited fields-see #7 below), radioisotope, immunotherapy or experimental agent and enrollment onto the study. Note: Patients on hormone or estrogen therapy and steroids for treatment of their disease may remain on therapy.
• A minimum of 7 days must have elapsed between a single fraction of ≤ 800 cGy to a limited field or conventional radiotherapy to a limited non marrow-bearing field such as an extremity or orbit and enrollment onto the study.
• Recovery from all toxicities of prior therapy including chemotherapy, radiation therapy, immunotherapy and experimental agents to ≤ grade 2 by NCI CTCAE, version 3.0.
• If not treated with bilateral orchiectomy, patients with HRPC must be willing to continue luteinizing hormone releasing hormone (LHRH) analogues throughout the study.
• If taking opioid medication, patient must be willing to continue on the same opioid medication that they are on at enrollment through the PK/ECG evaluations during Cycle 1.
• Karnofsky score of ≥60%.
• Various laboratory requirements.
• Must be willing to use effective contraception during and for 3 months following treatment if of child bearing potential.
• Must be willing to undergo pharmacokinetic blood draws and frequent ECG monitoring on Days 1 and 2 of Cycle 1.
• Must provide written, informed consent.

You may not qualify if:

• More than three cytotoxic chemotherapy regimens.
• Current treatment with any anticancer agent including but not limited to trastuzumab, aromatase inhibitors, or tamoxifen. Steroids, bisphosphonates and female hormone replacement therapy are allowed.
• Documented central nervous system (CNS) metastasis or carcinomatous meningitis.
• For patients in Cohorts 6 and 7, prior history of a serious allergic reaction to docetaxel; any chemotherapy containing Cremophor EL (used in drugs such as cyclosporine, etoposide, teniposide); or polysorbate 80 (the diluent for docetaxel).
• Current pregnancy or lactation.
• Current second malignancy except for non melanoma skin cancers, superficial bladder cancer, early cervical cancer or early prostate cancer not requiring treatment.
• Uncontrolled and/or serious medical conditions such as, but not limited to, active infection, symptomatic congestive heart failure, unstable angina, significant cardiac arrhythmia, significant neurological dysfunction, history of myocardial infarction or stroke within the 3 months prior to enrollment or any other condition which the Investigator feels would preclude protocol therapy.
• Concomitant participation in another clinical trial of an experimental drug, vaccine or device.
• Prior high dose chemotherapy requiring stem cell rescue.
• Atrial fibrillation, left bundle branch block, or obligatory use of a cardiac pacemaker.
• Currently on a drug known to increase the QTc duration.

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (3)

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Center

Hamilton, Ontario, L8V 5C2, Canada

Location

Related Publications (1)

• Chi KN, Yu EY, Jacobs C, Bazov J, Kollmannsberger C, Higano CS, Mukherjee SD, Gleave ME, Stewart PS, Hotte SJ. A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castration-resistant prostate cancer and other advanced cancers. Ann Oncol. 2016 Jun;27(6):1116-1122. doi: 10.1093/annonc/mdw068. Epub 2016 Feb 18.

  PMID: 27022067 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

apatorsen; Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Kim Chi, M.D.

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2007
• First Posted: June 19, 2007
• Study Start: June 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: October 1, 2011
• Last Updated: January 18, 2016

Record last verified: 2014-04

Locations

US (1); CA (2)