Details
Title NUA Randomized Phase 2 Study Comparing Docetaxel Alone to Docetaxel in Combination with OGX-427 in Patients with Relapsed or Refractory Metastatic Urothelial Carcinoma after Receiving a Platinum-containing Regimen Hoosier Oncology Group GU12-160; The Borealis-2 Clinical Trial
IRB HOG 1813
CC 13-554
Hospital Main Campus
Phase Phase 2
Disease Bladder, Genitourinary
Drug Docetaxel, OGX-427
Description
Primary Objective- To determine whether docetaxel administered in combination with OGX-427 provides a survival benefit compared to docetaxel alone.
- To compare the safety and tolerability of OGX-427 in combination with docetaxel to that of docetaxel alone.
- To compare overall response rate (ORR) (complete response [CR] + partial response [PR]), disease control rate (CR+PR+stable disease), duration of response, (see Section 10.3.7), and progression-free survival (PFS) between the treatment arms.
- To evaluate the effect of therapy with docetaxel and OGX-427 on serum Hsp27 levels and other serum proteins and explore their relation with clinical outcomes.
- To evaluate the association of urothelial carcinoma expression of Hsp27 measured by immunohistochemistry (IHC) in archival tissue with clinical outcomes.
- To evaluate the effect of therapy on peripheral blood circulating tumor cells (CTC) enumeration and expression of Hsp27 and other relevant proteins, via immunoflourescence, and levels of telomerase by quantitative PCR and explore their relation with clinical outcomes.
- Somatic (tumor) and germ-line DNA/ RNA will be isolated to allow future approved investigations to determine if somatic mutations in Hsp27, ABCB1, ABCG2, TUBB4 and other relevant genes of interest are associated with treatment outcome (optional informed consent).
Inclusion Criteria
- Participants must have a diagnosis of metastatic or inoperable, locally-advanced urothelial carcinoma (bladder, urethra, ureter and renal pelvis) (T4b, N2, N3, or M1 disease). NOTE: Mixed histological 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 any small cell features (mixed or pure histology) are not eligible.
- Participants must have measurable disease defined as at least one target lesion that can be accurately measured in at least one dimension by RECIST v1.1 criteria (see Appendix A). Lesions in previously irradiated areas should not be selected as target lesions, unless there is demonstrated progression in the lesion.
- Participants must have received prior systemic platinum-based chemotherapy for urothelial carcinoma. Specifically, subjects must also meet one or more of the following criteria:
- Initial metastatic recurrence < 1 year after the completion of perioperative therapy (i.e. neoadjuvant or adjuvant setting) and no more than one chemotherapy regimen administered in the metastatic or inoperable, locally advanced setting.
OR
- Initial metastatic recurrence > 1 year after the completion of perioperative therapy (i.e. neoadjuvant or adjuvant setting) with disease progression after the completion of at least one but no more than two chemotherapy regimens administered in the metastatic or inoperable, locally-advanced setting.
OR
- Disease progression after the completion of therapy administered in the metastatic or inoperable, locally advanced setting with no prior history of perioperative platinum-based therapy and no more than two chemotherapy regimens administered in the metastatic or inoperable, locally advanced setting.
- Initial metastatic recurrence < 1 year after the completion of perioperative therapy (i.e. neoadjuvant or adjuvant setting) and no more than one chemotherapy regimen administered in the metastatic or inoperable, locally advanced setting.
- Participants must be ≥ 18 years of age at time of consent since no dosing or adverse event data are currently available on the use of OGX-427 in participants < 18 years of age.
- Life expectancy of 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix B).
- Participants must have adequate organ and marrow function as defined below:
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Hemoglobin ≥ 8 g/dL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.1 X ULN (≤ 2.0 X ULN if secondary to Gilbert's disease)
- SGOT (AST)/SGPT (ALT) ≤ 1.5 X ULN
- Serum creatinine ≤ 1.5 X ULN
- 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 and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment and for three months after completion of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Ability to understand and the willingness to sign a written informed consent document.
NOTE: A woman of child-bearing potential is defined as a woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
Exclusion Criteria
- History of treatment with docetaxel or cabazitaxel 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 participant 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, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Cerebrovascular accident, myocardial infarction 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.