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

STATUS: Recruiting

Phase: 2

Diagnosis: Kidney Cancer

NCT ID: NCT01780545 (View complete trial on ClinicalTrials.gov)

DFCI Protocol ID: 13-106

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.

Conducting Institutions:

Dana-Farber Cancer Institute, Brigham and Women's Hospital

Overall PI:

Toni Choueiri, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:


Dana-Farber Cancer Institute: Amanda Fredericks, 617-632-5514, acfredericks@partners.org

Dana-Farber Cancer Institute: Meghara Walsh, 617-632-5264, mwalsh10@partners.org

Dana-Farber Cancer Institute: Judith Prisby, 617-632-5068, jprisby@partners.org

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 or 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

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.