Phase 2 Study of Docetaxel +/- OGX-427 in Patients With Relapsed or Refractory Metastatic Bladder Cancer

NCT01780545 | Completed Phase 2 Results DMC

• 1 other identifier: GU12-160
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 35

Brief Summary

This is a randomized, open-label Phase 2 clinical trial to evaluate whether suppression of Hsp27 (Heat shock protein 27) production using OGX-427, a second-generation antisense oligonucleotide (ASO), in combination with docetaxel can prolong survival time compared to docetaxel alone in participants with locally advanced or metastatic urothelial carcinoma (UC) that are relapsed or refractory after receiving a platinum-containing regimen.

Conditions

Bladder Cancer; Urothelial Carcinoma

Keywords

OGX-427; Docetaxel

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  To determine whether docetaxel administered in combination with OGX-427 provides a survival benefit compared to docetaxel alone.

  36 Months

Secondary Outcomes (5)

• Safety and Toxicity of Regimen

  36 Months

• Overall Response Rate

  Every 6 weeks

• Overall Survival (OS) According to Baseline Serum Hsp27 Level.

  36 months

• Hsp27 Expression in Archival Tissue

  Cycle 1

• Effect of Therapy Regimen on Circulating Tumor Cells (CTCs)and Correlative Analysis of Telomerase Activity

  Prior to screening, prior to first loading dose, and prior to cycles 1, 2, 3 and 5

Study Arms (2)

Experimental Arm: Arm A

EXPERIMENTAL

Three doses of 600 mg OGX-427 will be administered IV during the loading dose period (days -9 to -1). Following completion of the loading dose period, 600 mg OGX-427 will be given IV weekly on days 1, 8, and 15 of each 21-day cycle.

Drug: OGX-427; Drug: Docetaxel

Control Arm: Arm B

ACTIVE COMPARATOR

Docetaxel (75 mg/M2) will be administered IV on day 1 of each 21 day cycle for a maximum of 10 cycles.

Drug: Docetaxel

Interventions

OGX-427 DRUG

Three doses of 600 mg OGX-427 will be administered IV during the loading dose period (days -9 to -1). Following completion of the loading dose period, 600 mg OGX-427 will be given IV weekly on days 1, 8, and 15 of each 21-day cycle. OGX-427 must be administered prior to docetaxel on day 1 of each cycle. Following completion of 10 cycles of docetaxel, 600 mg OGX-427 will continue to be administered by IV weekly as maintenance therapy in Arm A participants who do not have disease progression (i.e., stable disease or better). Participants without documented disease progression who have discontinued from study treatment not due to toxicity related to OGX-427 can also continue to receive OGX-427 maintenance as long as they have completed disease assessments following at least 2 cycles of chemotherapy. Maintenance with OGX-427 will continue until disease progression or unacceptable toxicity.

Experimental Arm: Arm A

Docetaxel DRUG

For Arm A Only: Docetaxel should be administered immediately following the completion of the OGX-427 infusion. For Both Arms: Docetaxel (75 mg/M2) will be administered IV on Day 1 of each 21 day cycle for a maximum of 10 cycles.

Control Arm: Arm B; Experimental Arm: Arm A

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically documented metastatic or locally inoperable advanced urothelial carcinoma (bladder, urethra, ureter and renal pelvis) (T4b, N2, N3, or M1 disease. NOTE: Aberrant differentiation such as squamous, glandular (adenocarcinoma), and micropapillary are eligible unless the tumor is considered a pure histological variant according to the pathology report. Participants with small cell histology are not eligible.
• Participants must have measurable disease defined as at least one target lesion that has not been irradiated and can be accurately measured in at least one dimension by RECIST v1.1 criteria.
• Participants must have received prior systemic chemotherapy treatment for metastatic urothelial carcinoma. NOTE: Up to 2 prior systemic chemotherapeutic regimens given in the metastatic disease setting for urothelial carcinoma are allowed.
• Specifically, subjects must meet one or more of the following criteria:
• Progression during or after treatment with a regimen that includes a platinum salt (e.g., carboplatin or cisplatin) OR
• Disease recurrence within one year after neoadjuvant or adjuvant platinum-based systemic chemotherapy, measured from the date of last dose of chemotherapy or surgery until the day the informed consent is signed
• Participants must be ≥18 years since no dosing or adverse event data are currently available on the use of OGX-427 in participants \<18 years of age.
• Minimum of 21 days have elapsed since prior major surgery, with recovery from any adverse events.
• Minimum of 14 days have elapsed since any prior radiation therapy, with recovery from any adverse events.
• The effects of OGX-427 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• History of treatment with docetaxel in any setting. Participants treated with prior paclitaxel are eligible.
• Prior enrollment in the OncoGenex Phase 2 Study OGX-427-02.
• Participants may not be receiving other investigational agents.
• Participants with known brain or spinal cord metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. NOTE: Brain imaging is not required unless the patient has symptoms or physical signs of central nervous system (CNS) disease.
• History of allergic reactions or severe hypersensitivity reactions to drugs formulated with polysorbate 80 or antisense oligonucleotides.
• Peripheral neuropathy ≥Grade 2.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
• Cerebrovascular accident or pulmonary embolus within 3 months of randomization.
• Pregnant women and breast feeding women are excluded from this study because of the risk to a fetus due to docetaxel chemotherapy and OGX-427 systemic treatment (fertility toxicology studies have not been completed for OGX-427).
• Active second malignancy (except non-melanomatous skin cancer or incidental prostate cancer found on cystectomy): active secondary malignancy is defined as a current need for cancer therapy or a high possibility (\>30%) of recurrence during the study.

Sponsors & Collaborators

• Noah Hahn, M.D.: lead
• Achieve Life Sciences: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (35)

University of Alabama Hematology Oncology Clinic at Medical West

Birmingham, Alabama, 35294, United States

Location

City of Hope: Duarte

Duarte, California, 91010, United States

Location

City of Hope: Antelope Valley

Lancaster, California, 93534, United States

Location

USC: Norris Comprehensive Cancer Center

Los Angeles, California, 90089, United States

Location

UCLA: Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

IU Health Goshen Hospital

Goshen, Indiana, 46527, United States

Location

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, 46219, United States

Location

IU Health at Ball Memorial Hospital

Muncie, Indiana, 47303, United States

Location

University of Maryland: Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68114, United States

Location

Dartmouth-Hitchcock Medical Center: Norris Cotton Cancer Center

Manchester, New Hampshire, 03102, United States

Location

Memorial Sloan-Kettering Cancer Center: Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

John Theurer Cancer Center: Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of New Mexico Cancer Center: Albuquerque

Albuquerque, New Mexico, 87131, United States

Location

University of New Mexico Cancer Center: Las Cruces

Las Cruces, New Mexico, 88011, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan-Kettering Cancer Center: Commack

Commack, New York, 11725, United States

Location

New York University Clinical Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center: Main Campus

New York, New York, 10065, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Memorial Sloan-Kettering Cancer Center: Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan-Kettering Cancer Center: Sleepy Hollow

Sleepy Hollow, New York, 10591, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic: Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Lake Health: University Hospitals Seidman Cancer Center

Mentor, Ohio, 44060, United States

Location

UHHS Chagrin Highlands: Seidman Cancer Center

Orange, Ohio, 44122, United States

Location

Thomas Jefferson University: Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

MUSC Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (3)

• Jonathan E. Rosenberg, Noah M. Hahn, Meredith M. Regan, Cindy Jacobs, Patricia S. Stewart, Toni K. Choueiri. The Borealis-2 clinical trial: A randomized phase II study of OGX-427 plus docetaxel versus docetaxel alone in relapsed/refractory metastatic urothelial cancer. J Clin Oncol 31, 2013 (suppl; abstr TPS4588^) http://abstracts2.asco.org/AbstView_132_114639.html

  BACKGROUND

• Choueiri TK, Hahn NM, Pal SK, Alva AS, Dreicer R, Starodub A, Sonpavde G, Hoffman-Censits JH, Picus J, Balar AV, Guancial EA, Regan MM, Jacobs C, Stewart PS, Rosenberg JE. The Borealis-2 clinical trial: A randomized phase 2 study of OGX-427 (apatorsen) plus docetaxel versus docetaxel alone in relapsed/refractory metastatic urothelial cancer. J Clin Oncol 32:5s, 2014 (suppl; abstr TPS4593^)

  BACKGROUND

• Choueiri TK, Hahn NM, Alva AS, Lauer RC, Dreicer R, Picus J, Pili R, Balar AV, Sonpavde G, Hoffman-Censits JH, Guancial EA, Alter R, Regan MM, Jacobs C, Stewart PS, Pal SK, Rosenberg JE. The Borealis-2 clinical trial: A randomized phase 2 study of OGX-427 (Apatorsen) plus docetaxel versus docetaxel alone in relapsed/refractory metastatic urothelial cancer. J Clin Oncol 33:5s, 2015 (suppl; abstr TPS4577)

  BACKGROUND

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

apatorsen; Docetaxel

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Data Manager
• Organization: Hoosier Cancer Research Network

hcrndm@hoosiercancer.org

3176345842

Study Officials

• Noah Hahn, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: January 31, 2013
• Study Start: April 1, 2013
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: July 11, 2022
• Results First Posted: November 14, 2017

Record last verified: 2022-07

Locations

US (35)