Clinical trial NCT01454089: A Phase 2 Study Comparing Chemotherapy in Combination With OGX-427 or Placebo in Patients With Bladder Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urologic Neoplasms
Metastatic Bladder Cancer
Urinary Tract Neoplasms
Keywords: bladder
urinary tract
transitional cell carcinoma
metastatic bladder cancer
chemotherapy
Lead sponsor: Achieve Life Sciences
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2011-10-18
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 All participants have an End of Treatment (EOT) visit when they are withdrawn from all study treatment (chemotherapy and maintenance).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

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline to date of death by any cause (up to approximately 12 months)
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (AEs), Serious AEs, and Grade 3 or Higher AEs
timeFrame: From initiation of study drug to end of study (up to 8 months)
measure: Number of Participants With ≥ 1 Hematology Abnormality and ≥ 1 Grade 3 or Higher Hematology Abnormality
timeFrame: Screening through End of Study Visit (Within 30 [±7] days following withdrawal of study treatment)
measure: Number of Participants With ≥ 1 Chemistry Laboratory Abnormality and ≥ 1 Grade 3 or Higher Chemistry Laboratory Abnormality
timeFrame: Screening through End of Study Visit (Within 30 [±7] days following withdrawal of study treatment)
measure: Number of Participants With ≥ 1 Urinalysis Abnormality and ≥ 1 Grade 3 or Higher Urinalysis Abnormality
timeFrame: Screening through End of Study Visit (Within 30 [±7] days following withdrawal of study treatment)
measure: Best Objective Tumor Response
timeFrame: Baseline to measured progressive disease (up to approximately 12 months)
measure: Overall Response Rate (ORR) and Disease Control Rate
timeFrame: Baseline to measured progressive disease (up to approximately 12 months)
measure: Duration of Overall Response Rate
timeFrame: Baseline to measured progressive disease (up to approximately 12 months)
measure: Progression-free Survival (PFS)
timeFrame: Baseline to measured progressive disease (up to approximately 12 months)
measure: Change From Baseline in Serum Hsp27 levels by End of Treatment
timeFrame: Baseline, End of Treatment (up to approximately 12 months)
measure: Change From Baseline in Serum Clusterin Levels by End of Treatment
timeFrame: Baseline, End of Treatment (up to approximately 12 months)
measure: Change From Baseline in Circulating Tumor Cell (CTC) Count by End of Treatment
timeFrame: Baseline, End of Treatment (up to approximately 12 months)
measure: Serum OGX-427 Cmax and Trough Levels
timeFrame: Cycle 1 Day 1 through Cycle 6 Day 1, End of Treatment (up to approximately 12 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: St. Louis
country: United States
facility: Siteman Cancer Center, Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Urology Cancer Center and GU Research Network
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Medical Center, Albert Einstein College of Medicine
state: New York
city: Lake Success
country: United States
facility: Monter Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Center
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Oshawa
country: Canada
facility: R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM-Hospital Notre Dame
state: Quebec
city: Bretonneau Tours
country: France
facility: Centre Hospitalier Régional et Universitaire - Hôpital
state: Centre
city: Reims
country: France
facility: Institute Jean Godinot
state: Champagne-Ardenne
city: Rouen
country: France
facility: Centre Hospitalier Universitaire de Rouen
state: Haute-Normandie
city: Villejuif Cedex
country: France
facility: Centre Hospitalier Universitaire, Institut Gustave Roussy
state: Ile-de-france
city: Angers Cedex 9
country: France
facility: Centre Paul Papin
state: Pays De La Loire
city: St. Herblain Cedex
country: France
facility: Medicale Centre René Gauducheau
state: Pays de la Loire
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
state: Provence Alpes Cote D'Azur
city: Nice
country: France
facility: Centre Antoine Lacassagne
state: Provence Alpes Cote d'Azur
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Wuerttemberg
city: München
country: Germany
facility: Klinikum Rechts der Isar der Technischen Universität
state: Bayern
city: Frankfurt
country: Germany
facility: Johann-Wolfgang-Goethe-Universität Frankfurt
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedeersachen
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
state: Saarland
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg A.ö.R.
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden
state: Sachsen
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thuringen
city: Mainz
country: Germany
facility: Universitätsklinikum Mainz
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico di Modena
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo Pavia
city: Roma
country: Italy
facility: Unità Operativa di Oncologia Medica
city: Wroclaw
country: Poland
facility: Akademicki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy
state: Kujawsko-Pomorskie
city: Otwock
country: Poland
facility: NZOZ Europejskie Centrum Zdrowia Otwock
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im. M. Sklodowskiej-Curie
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Olsztyn
country: Poland
facility: Zaklad Opieki Zdrowotnej MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
state: Warminski-Mazurskie
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebrón
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Institut Català D'Oncologia, Hospital Duran i Reynals
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología-Fundación (IVO-FINCIVO)
Study officials:
affiliation: Columbia University
name: Daniel Petrylak, MD
role: PRINCIPAL_INVESTIGATOR
References: