Phase 2 Study of Docetaxel +/- OGX-427 in Patients With Relapsed or Refractory Metastatic Bladder Cancer
Condition: Bladder Cancer; Urothelial Carcinoma
MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell
Intervention: OGX-427; Docetaxel
Intervention description: 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.; 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 MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 200.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: OGX-427; Docetaxel

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.
    

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.