A Randomized, Double-blind Phase 2 Study Comparing Gemcitabine and Cisplatin in Combination With OGX-427 or Placebo in Patients With Advanced Transitional Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- OGX-427 600 mg
- Conditions
- Urologic Neoplasms
- Sponsor
- Achieve Life Sciences
- Enrollment
- 183
- Locations
- 55
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The primary objective of this study is to ascertain whether there is evidence of longer survival relative to the control arm for three comparisons: 600 mg OGX-427 Arm to control Arm; 1000 mg OGX-427 Arm to control Arm; and pooled 600 mg and 1000 mg OGX-427 Arms to control Arm.
Detailed Description
Following 3 loading doses, participants receive chemotherapy and study drug on a 21-day cycle during the Treatment Period (Chemotherapy Period) until disease progression, completion of 6 cycles, toxicity or voluntary participant withdrawal. Participants who do not have documented disease progression and have completed a minimum of four cycles of chemotherapy continue to receive weekly Study Drug maintenance therapy during the Maintenance Period until disease progression or the participant fulfills one of the other reasons for withdrawal from protocol treatment, unless they have been discontinued from protocol treatment for unacceptable toxicity related to study drug. All participants have an End of Treatment (EOT) visit when they are withdrawn from all study treatment (chemotherapy and maintenance). All participants are followed until documented disease progression. Once disease progression is documented, participants enter a Survival Follow-up Period during which data are collected regarding further cancer therapy, secondary malignancy, and survival status.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years at the time of consent
- •Histologically documented metastatic or locally inoperable advanced transitional cell carcinoma (TCC) of the urinary tract (bladder, urethra, ureter and renal pelvis) (T4b, N2, N3 or M1 disease) NOTE: Certain mixed histologies that are predominately (≥ 50%) TCC are eligible: squamous, adenocarcinoma, and undifferentiated. Mixed undifferentiated histology requires immunohistochemistry (IHC) consistent with a TCC origin. Mixed small-cell histologies are excluded
- •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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- •No prior systemic chemotherapy with the following exceptions:
- •Prior use of radiosensitizing single agent therapy is allowed
- •Prior neoadjuvant and adjuvant chemotherapy may be allowed
- •Minimum of 21 days since prior major surgery or radiation therapy
- •Karnofsky performance status ≥ 70%
- •Required laboratory values at baseline:
- •absolute neutrophil count (ANC) ≥ 1.5 x 10\^9 cells/L
Exclusion Criteria
- •A candidate for potential curative surgery or radiotherapy
- •Intravesical therapy within the last 3 months
- •Documented brain metastasis or carcinomatous meningitis, treated or untreated. NOTE: Brain imaging is not required unless the patient has symptoms or physical signs of central nervous system (CNS) disease.
- •Peripheral neuropathy ≥ Grade 2
- •Known serious hypersensitivity to gemcitabine, cisplatin or carboplatin
- •Current serious, uncontrolled medical condition such as congestive heart failure, angina, hypertension, arrhythmia, diabetes mellitus, infection, etc. or any condition such as a psychiatric illness which in the opinion of the investigator would make the patient unacceptable for the protocol
- •Cerebrovascular accident, myocardial infarction or pulmonary embolus within 6 months of randomization
- •Active second malignancy (except non-melanomatous skin cancer): active secondary malignancy is defined as a current need for cancer therapy or a high possibility (\> 30%) of recurrence during the study
- •Pregnant or nursing (must have a negative serum or urine pregnancy test within 72 hours prior to randomization)
- •Participating in a concurrent clinical trial of an experimental drug, vaccine or device. Participation in an observational study is allowed
Arms & Interventions
OGX-427 600 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (600 mg)
Intervention: OGX-427 600 mg
OGX-427 600 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (600 mg)
Intervention: Gemcitabine
OGX-427 600 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (600 mg)
Intervention: Cisplatin
OGX-427 600 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (600 mg)
Intervention: Carboplatin
OGX-427 1000 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (1000 mg)
Intervention: OGX-427 1000 mg
OGX-427 1000 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (1000 mg)
Intervention: Gemcitabine
OGX-427 1000 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (1000 mg)
Intervention: Cisplatin
OGX-427 1000 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (1000 mg)
Intervention: Carboplatin
Placebo
Standard chemotherapy (gemcitabine and cisplatin) in combination with placebo
Intervention: Placebo
Placebo
Standard chemotherapy (gemcitabine and cisplatin) in combination with placebo
Intervention: Gemcitabine
Placebo
Standard chemotherapy (gemcitabine and cisplatin) in combination with placebo
Intervention: Cisplatin
Placebo
Standard chemotherapy (gemcitabine and cisplatin) in combination with placebo
Intervention: Carboplatin
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Baseline to date of death by any cause (up to approximately 12 months)
OS is defined as the time from randomization to death from any cause; OS was censored on date of last contact for participants still alive at time of analysis.
Secondary Outcomes
- Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and Grade 3 or Higher AEs(From initiation of study drug to end of study (up to 8 months))
- Number of Participants With ≥ 1 Hematology Abnormality and ≥ 1 Grade 3 or Higher Hematology Abnormality(Screening through End of Study Visit (Within 30 [±7] days following withdrawal of study treatment))
- Number of Participants With ≥ 1 Chemistry Laboratory Abnormality and ≥ 1 Grade 3 or Higher Chemistry Laboratory Abnormality(Screening through End of Study Visit (Within 30 [±7] days following withdrawal of study treatment))
- Number of Participants With ≥ 1 Urinalysis Abnormality and ≥ 1 Grade 3 or Higher Urinalysis Abnormality(Screening through End of Study Visit (Within 30 [±7] days following withdrawal of study treatment))
- Best Objective Tumor Response(Baseline to measured progressive disease (up to approximately 12 months))
- Overall Response Rate (ORR) and Disease Control Rate(Baseline to measured progressive disease (up to approximately 12 months))
- Duration of Overall Response Rate(Baseline to measured progressive disease (up to approximately 12 months))
- Progression-free Survival (PFS)(Baseline to measured progressive disease (up to approximately 12 months))
- Change From Baseline in Serum Hsp27 levels by End of Treatment(Baseline, End of Treatment (up to approximately 12 months))
- Change From Baseline in Serum Clusterin Levels by End of Treatment(Baseline, End of Treatment (up to approximately 12 months))
- Change From Baseline in Circulating Tumor Cell (CTC) Count by End of Treatment(Baseline, End of Treatment (up to approximately 12 months))
- Serum OGX-427 Cmax and Trough Levels(Cycle 1 Day 1 through Cycle 6 Day 1, End of Treatment (up to approximately 12 months))