A Phase 2 Study Comparing Chemotherapy in Combination With OGX-427 or Placebo in Patients With Bladder Cancer

Achieve Life Sciences183 enrolled

Overview

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.

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 All participants have an End of Treatment (EOT) visit when they are withdrawn from all study treatment (chemotherapy and maintenance).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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

183

Conditions

Urologic Neoplasms Metastatic Bladder Cancer Urinary Tract Neoplasms

Interventions

OGX-427 600 mgDRUG

Patients will receive three loading doses of 600 mg Study Drug within a 9-day period. Following the loading dose period, patients will receive weekly Study Drug infusions (600 mg IV) on Days 1, 8 and 15 of each 21-day cycle.

OGX-427 1000 mgDRUG

Patients will receive three loading doses of 600 mg Study Drug within a 9-day period. Following the loading dose period, patients will receive weekly Study Drug infusions (1000 mg IV) on Days 1, 8 and 15 of each 21-day cycle.

PlaceboDRUG

Patients will receive three loading doses of placebo within a 9-day period. Following the loading dose period, patients will receive weekly placebo infusions (IV) on Days 1, 8 and 15 of each 21-day cycle.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years at the time of consent 2. 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 3. 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 4. 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 5. Minimum of 21 days since prior major surgery or radiation therapy 6. Karnofsky performance status ≥ 70% 7. Required laboratory values at baseline: * absolute neutrophil count (ANC) ≥ 1.5 x 10\^9 cells/L * platelet count ≥ 125 x 10\^9/L * calculated creatinine clearance ≥ 60 mL/minute * bilirubin ≤ 1.5 x upper limit of normal (ULN; ≤ 2.5 x ULN if secondary to Gilbert's disease) * aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN 8. If of child-bearing potential, willing to use contraceptives 9. Willing to give written informed consent Exclusion Criteria: 1. A candidate for potential curative surgery or radiotherapy 2. Intravesical therapy within the last 3 months 3. 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. 4. Peripheral neuropathy ≥ Grade 2 5. Known serious hypersensitivity to gemcitabine, cisplatin or carboplatin 6. 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 7. Cerebrovascular accident, myocardial infarction or pulmonary embolus within 6 months of randomization 8. 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 9. Pregnant or nursing (must have a negative serum or urine pregnancy test within 72 hours prior to randomization) 10. Participating in a concurrent clinical trial of an experimental drug, vaccine or device. Participation in an observational study is allowed

Locations (55)

Outcomes

Primary Outcomes

Overall Survival (OS)

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.

Time frame: Baseline to date of death by any cause (up to approximately 12 months)

Secondary Outcomes

Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and Grade 3 or Higher AEs

Treatment-emergent AEs are defined as and AE that occurred after the first dose of study drug up to 30 days after the last dose of study drug. AEs were graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment-emergent AEs could have occurred during loading dose period, chemotherapy period, maintenance period, and treatment period A detailed summary of adverse events is located in the Reported Adverse Event Module.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Screening through End of Study Visit (Within 30 [±7] days following withdrawal of study treatment)

Best Objective Tumor Response

Complete Response (CR): Complete disappearance of all measurable and non-measurable disease with no new lesions. Any pathological lymph node (target or non-target) must have a reduction in short axis to \< 10 mm). All markers of disease must have normalized. Partial Response (PR): A decrease from baseline of ≥ 30% of the diameter(s) of all target measurable lesions with no unequivocal progression of non-measurable lesions and no new lesions. Stable Disease (SD): Does not qualify for CR, PR, or progression. Disease Progression (PD): If at least one of following criteria is met: 1. Appearance of any new lesion or site of disease. 2. A 20% increase in the sum of the diameter(s) of target measurable lesions over either the smallest sum observed or over baseline if no decrease during therapy has occurred. The sum must also demonstrate an absolute increase of at least 5 mm. 3. Unequivocal progression of non-target lesions alone.

Data from ClinicalTrials.gov

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