Phase 2 Study of Docetaxel +/- OGX-427 in Patients With Relapsed or Refractory Metastatic Bladder Cancer
Conditions
Bladder Cancer - Urothelial Carcinoma
Conditions: official terms
Carcinoma, Transitional Cell - Urinary Bladder Neoplasms
Conditions: Keywords
OGX-427, Docetaxel
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: OGX-427 Type: Drug
Name: Docetaxel Type: Drug
Overall Status
Recruiting
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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.
Locations
University of Alabama Hematology Oncology Clinic at Medical West
Birmingham, Alabama, United States
Status: Recruiting
Contact: Guru Sonpavde, M.D. - sonpavde@uab.edu
City of Hope: Duarte
Duarte, California, United States
Status: Recruiting
Contact: Sumanta Pal, M.D. - spal@coh.org
City of Hope: Antelope Valley
Lancaster, California, United States
Status: Recruiting
Contact: Sumanta Pal, M.D. - spal@coh.org
UCLA: Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Status: Recruiting
Contact: Steven Wong, M.D. - sgwong@mednet.ucla.edu
USC: Norris Comprehensive Cancer Center
Los Angeles, California, United States
Status: Not yet recruiting
Contact: David Quinn, M.D. - diquinn@usc.edu
IU Health Goshen Hospital
Goshen, Indiana, United States
Status: Recruiting
Contact: Alex Starodub, M.D. - 574-535-2886 - astarodub@iuhealth.org
Indiana University Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, United States
Status: Recruiting
Contact: Costantine Albany, M.D. - calbany@iu.edu
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States
Status: Recruiting
Contact: Bamidele Adensunloye, M.D. - 317-859-5500 - badesunloye@IUHealth.org
IU Health at Ball Memorial Hospital
Muncie, Indiana, United States
Status: Recruiting
Contact: William Fisher, M.D. - 765-281-2174 - wfisher1@iuhealth.org
Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Status: Recruiting
Contact: Noah Hahn, M.D. - 443-287-0553 - nhahn4@jhmi.edu
University of Maryland: Greenebaum Cancer Center
Baltimore, Maryland, United States
Status: Recruiting
Contact: Arif Hussain, M.D. - 410-328-7226 - ahussain@som.umaryland.edu
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Status: Recruiting
Contact: Toni Choueiri, MD - 617-632-4524 - Toni_Choueiri@dfci.harvard.edu
University of Michigan Cancer Center
Ann Arbor, Michigan, United States
Status: Recruiting
Contact: Ajjai Alva, MB, BS - 734-647-8903 - ajjai@med.umich.edu
Siteman Cancer Center
St. Louis, Missouri, United States
Status: Recruiting
Contact: Joel Picus, M.D. - 314-747-1367
Nebraska Cancer Specialists
Omaha, Nebraska, United States
Status: Recruiting
Contact: Ralph Hauke, M.D. - 402-354-8124 - rhauke@nebraskacancer.com
Dartmouth-Hitchcock Medical Center: Norris Cotton Cancer Center
Manchester, New Hampshire, United States
Status: Recruiting
Contact: Sergey Devitskiy, M.D. - 603-650-5534 - Sergey.Devitskiy@hitchcock.org
Memorial Sloan-Kettering Cancer Center: Basking Ridge
Basking Ridge, New Jersey, United States
Status: Recruiting
Contact: Jonathan Rosenberg, MD - 646-422-4461 - rosenbj1@mskcc.org
John Theurer Cancer Center: Hackensack University Medical Center
Hackensack, New Jersey, United States
Status: Recruiting
Contact: Robert Alter, M - 551-996-5072 - ralter@hackensackumc.org
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Status: Recruiting
Contact: Mark Stein, M.D. - steinmn@cinj.rutgers.edu
University of New Mexico Cancer Center: Albuquerque
Albuquerque, New Mexico, United States
Status: Recruiting
Contact: Richard Lauer, M.D. - rlauer@salud.unm.edu
University of New Mexico Cancer Center: Las Cruces
Las Cruces, New Mexico, United States
Status: Recruiting
Contact: William Adler, M.D. - 575-521-1554 - William.Adler@lpnt.net
Roswell Park Cancer Institute
Buffalo, New York, United States
Status: Recruiting
Contact: Roberto Pili, M.D. - roberto.pili@roswellpark.org
Memorial Sloan-Kettering Cancer Center: Commack
Commack, New York, United States
Status: Recruiting
Contact: Jonathan Rosenberg, MD - 646-422-4461 - rosenbj1@mskcc.org
Memorial Sloan-Kettering Cancer Center: Main Campus
New York, New York, United States
Status: Recruiting
Contact: Jonathan Rosenberg, MD - 646-422-4461 - rosenbj1@mskcc.org
New York University Clinical Cancer Center
New York, New York, United States
Status: Recruiting
Contact: Arjun Balar, M.D. - 212-731-5820 - arjun.balar@nyumc.org
University of Rochester Medical Center
Rochester, New York, United States
Status: Recruiting
Contact: Elizabeth Guancial, M.D. - Elizabeth_Guancial@urmc.rochester.edu
Memorial Sloan-Kettering Cancer Center: Rockville Centre
Rockville Centre, New York, United States
Status: Recruiting
Contact: Jonathan Rosenberg, MD - 646-422-4461 - rosenbj1@mskcc.org
Memorial Sloan-Kettering Cancer Center: Sleepy Hollow
Sleepy Hollow, New York, United States
Status: Recruiting
Contact: Jonathan Rosenberg, MD - 646-422-4661 - rosenbj1@mskcc.org
Cleveland Clinic: Taussig Cancer Institute
Cleveland, Ohio, United States
Status: Recruiting
Contact: Rob Dreicer, M.D. - 216-445-2360
University Hospitals Seidman Cancer Center
Cleveland, Ohio, United States
Status: Recruiting
Contact: Christopher Hoimes, D.O. - 216-844-3951 - cjh122@case.edu
Lake Health: University Hospitals Seidman Cancer Center
Mentor, Ohio, United States
Status: Recruiting
Contact: Christopher Hoimes, D.O. - 216-844-3951 - cjh122@case.edu
UHHS Chagrin Highlands: Seidman Cancer Center
Orange Village, Ohio, United States
Status: Recruiting
Contact: Christopher Hoimes, D.O. - 216-844-3951 - cjh122@case.edu
Thomas Jefferson University: Kimmel Cancer Center
Philadelphia, Pennsylvania, United States
Status: Recruiting
Contact: Jean Hoffman-Censits, M.D. - 215-955-8874 - jean.hoffman-censits@jefferson.edu
MUSC Hollings Cancer Center
Charleston, South Carolina, United States
Status: Recruiting
Contact: Harry Drabkin, M.D. - 843-792-9007 - drabkin@musc.edu
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Status: Recruiting
Contact: John Burfeind, M.D. - jburfeind@mcw.edu
Start Date
April 2013
Completion Date
July 2016
Sponsors
Noah Hahn, M.D.
Source
Hoosier Cancer Research Network
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page