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

NCT ID: NCT01780545

Last Updated: 2022-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2017-10-31

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.

Detailed Description

OUTLINE: This is a multi-center study.

Eligible patients will be stratified based on time from prior systemic chemotherapy (< 3 vs ≥ 3 months) and Bellmunt prognostic factors criteria, which include Eastern Cooperative Oncology Group (ECOG) performance status >0, hemoglobin <10g/dL, and presence of liver metastases (0 versus 1-3 risk factors). Within the strata, participants will be randomly assigned with equal probability to either the investigational arm (Arm A: docetaxel + OGX-427) or the control arm (Arm B: docetaxel alone).

INVESTIGATIONAL ARM OGX-427 + DOCETAXEL (Arm A):

LOADING DOSE PERIOD:

Participants randomized onto the investigational arm (Arm A) will receive OGX-427 beginning with a loading dose period prior to the initiation of docetaxel treatment. The first dose of OGX-427 for the loading dose period must be administered within 5 working days of registration and randomization.

During the loading dose period, participants will receive three separate administrations of 600 mg OGX-427 intravenously (IV) (days -9 to -1). There must be at least one "non-infusion" day between each administration of OGX-427 (i.e., every other day) during the loading dose period and between the third loading dose of OGX-427 and day 1 of cycle 1. There should be no more than 7 days between the last loading dose and day 1 of cycle 1.

TREATMENT PERIOD:

During the treatment period, participants randomized to this arm will receive:

• OGX-427 600 mg 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.
• Docetaxel (75 mg/M2) IV on day 1 of each 21-day cycle. Docetaxel should be administered immediately following the completion of the OGX-427 infusion.

OGX-427 MAINTENANCE:

Following completion of 10 cycles of docetaxel, 600 mg OGX-427 will continue to be administered by IV weekly as maintenance therapy for 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.

CONTROL ARM - DOCETAXEL ALONE (Arm B):

TREATMENT PERIOD:

During the treatment period, participants randomized to this arm will receive:

• Docetaxel (75 mg/M2) IV on day 1 of each 21-day cycle. The first dose of docetaxel must be administered within 5 working days of registration and randomization. Participants will continue to receive docetaxel on day 1 of each 21-day cycle until disease progression, unacceptable toxicity related to docetaxel, voluntary patient withdrawal, or a maximum of 10 docetaxel cycles.

FOLLOW-UP FOR BOTH ARMS:

Imaging studies will be performed every 6 weeks (i.e., after completion of cycles 2, 4, 6, 8 and 10) until disease progression and with any sign or symptom of new or worsening disease; computed tomography scan (CT) of chest/abdomen/pelvis is preferred but magnetic resonance imaging scan(MRI) is acceptable, especially for participants with increased risk of contrast-related nephropathy or other contraindications. For Arm A, scans will be performed every 2 cycles (6 weeks) +/1 week during the 21-day cycles of docetaxel administration and every 6 weeks during maintenance OGX-427 administration until disease progression; for Arm B, scans will be performed every 6 weeks during the 21-day cycles of docetaxel administration until disease progression. All scans should be completed before the subsequent cycle is scheduled to begin. Bone scans will be repeated, if positive at baseline, every 6 weeks during the first 4 cycles of treatment (i.e., at the end of cycles 2 and 4) and then every 12 weeks thereafter until disease progression (i.e., at the end of cycle 8, at end of treatment, and during maintenance with OGX-427 [Arm A only]).

All participants will have an End of Treatment (EOT) visit when they discontinue study treatment. All participants will be followed until documented disease progression.

Once disease progression is documented, participants will enter a survival follow-up period. All participants must be followed for survival as the primary endpoint. During the survival follow-up period, data will be collected every three months regarding further cancer therapy, secondary malignancy, and survival status.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Life Expectancy: Greater than 3 months

Hematopoietic:

• Absolute neutrophil count(ANC)≥ 1,500/mcL
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mcL

Hepatic:

• Bilirubin ≤ 1.1 x upper limit of normal (ULN) (≤ 2.0 x ULN if secondary to Gilbert's disease)
• Aspartate transaminase (AST), serum glutamic oxaloacetic transaminase (SGOT)/alanine transaminase (ALT), serum glutamic pyruvic transaminase (SGPT) ≤ 1.5 X institutional ULN

Renal:

• Serum creatinine ≤ 1.5 x ULN

Cardiac:

• Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or myocardial infarction within 3 months of randomization.

Conditions

Bladder Cancer; Urothelial Carcinoma

Study Design

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

Study Groups

Experimental Arm: Arm A

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.

Group Type: EXPERIMENTAL

OGX-427

Intervention Type: 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.

Docetaxel

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: 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.

Interventions

OGX-427

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.

Intervention Type: DRUG

Docetaxel

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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:

1. Progression during or after treatment with a regimen that includes a platinum salt (e.g., carboplatin or cisplatin) OR

2. 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.

Exclusion Criteria

• 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.

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

Sponsors

Achieve Life Sciences

INDUSTRY

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: collaborator

Noah Hahn, M.D.

OTHER

Sponsor Role: lead

Responsible Party

Noah Hahn, M.D.

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Noah Hahn, M.D.

Role: STUDY_CHAIR

Hoosier Cancer Research Network

Locations

University of Alabama Hematology Oncology Clinic at Medical West

Birmingham, Alabama, United States

City of Hope: Duarte

Duarte, California, United States

City of Hope: Antelope Valley

Lancaster, California, United States

USC: Norris Comprehensive Cancer Center

Los Angeles, California, United States

UCLA: Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

IU Health Goshen Hospital

Goshen, Indiana, United States

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, United States

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, United States

IU Health at Ball Memorial Hospital

Muncie, Indiana, United States

University of Maryland: Greenebaum Cancer Center

Baltimore, Maryland, United States

Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Siteman Cancer Center

St Louis, Missouri, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Dartmouth-Hitchcock Medical Center: Norris Cotton Cancer Center

Manchester, New Hampshire, United States

Memorial Sloan-Kettering Cancer Center: Basking Ridge

Basking Ridge, New Jersey, United States

John Theurer Cancer Center: Hackensack University Medical Center

Hackensack, New Jersey, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

University of New Mexico Cancer Center: Albuquerque

Albuquerque, New Mexico, United States

University of New Mexico Cancer Center: Las Cruces

Las Cruces, New Mexico, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan-Kettering Cancer Center: Commack

Commack, New York, United States

New York University Clinical Cancer Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center: Main Campus

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Memorial Sloan-Kettering Cancer Center: Rockville Centre

Rockville Centre, New York, United States

Memorial Sloan-Kettering Cancer Center: Sleepy Hollow

Sleepy Hollow, New York, United States

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

Cleveland Clinic: Taussig Cancer Institute

Cleveland, Ohio, United States

Lake Health: University Hospitals Seidman Cancer Center

Mentor, Ohio, United States

UHHS Chagrin Highlands: Seidman Cancer Center

Orange, Ohio, United States

Thomas Jefferson University: Kimmel Cancer Center

Philadelphia, Pennsylvania, United States

MUSC Hollings Cancer Center

Charleston, South Carolina, United States

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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

Reference Type: 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^)

Reference Type: 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)

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.hoosiercancer.org

Hoosier Cancer Research Network Website

Other Identifiers

GU12-160

Identifier Type: -

Identifier Source: org_study_id