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

NCT01454089 | Completed Phase 2

• 1 other identifier: OGX-427-02
• Study Type: interventional
• Target: 183
• Locations: 7 countries
• Sites: 55

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.

Conditions

Urologic Neoplasms; Metastatic Bladder Cancer; Urinary Tract Neoplasms

Keywords

bladder; urinary tract; transitional cell carcinoma; metastatic bladder cancer; chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (12)

• 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)

Study Arms (3)

OGX-427 600 mg

EXPERIMENTAL

Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (600 mg)

Drug: OGX-427 600 mg; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

OGX-427 1000 mg

EXPERIMENTAL

Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (1000 mg)

Drug: OGX-427 1000 mg; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

Placebo

ACTIVE COMPARATOR

Standard chemotherapy (gemcitabine and cisplatin) in combination with placebo

Drug: Placebo; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

Interventions

OGX-427 600 mg DRUG

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.

Also known as: apatorsen

OGX-427 600 mg

OGX-427 1000 mg DRUG

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.

Also known as: apatorsen

OGX-427 1000 mg

Placebo DRUG

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.

Placebo

Gemcitabine DRUG

Patients will receive gemcitabine (1000 mg/m\^2) for up to 6 cycles administered IV on Days 1 and 8 of each 21-day cycle following Study Drug infusion. The Cycle 1, Day 1 administration of chemotherapy must occur within 5 days of the third loading dose of Study Drug.

OGX-427 1000 mg; OGX-427 600 mg; Placebo

Cisplatin DRUG

Following the administration of gemcitabine on Day 1, cisplatin (70 mg/m\^2) will be administered IV for up to 6 cycles. The Cycle 1, Day 1 administration of chemotherapy must occur within 5 days of the third loading dose of Study Drug.

OGX-427 1000 mg; OGX-427 600 mg; Placebo

Carboplatin DRUG

Following the administration of gemcitabine on Day 1, cisplatin (70 mg/m\^2) is to be administered IV for up to 6 cycles; however, carboplatin could be substituted for cisplatin for some unacceptable toxicities. The Cycle 1, Day 1 administration of chemotherapy must occur within 5 days of the third loading dose of Study Drug.

OGX-427 1000 mg; OGX-427 600 mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• If of child-bearing potential, willing to use contraceptives

You may not qualify if:

• 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

Sponsors & Collaborators

• Achieve Life Sciences: lead
• PRA Health Sciences: collaborator

Study Sites (55)

City of Hope National Medical Center

Duarte, California, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, United States

Location

University of California Los Angeles

Los Angeles, California, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Location

Radiological Associates of Sacramento

Sacramento, California, United States

Location

Yale University

New Haven, Connecticut, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, United States

Location

Siteman Cancer Center, Washington University School of Medicine

St Louis, Missouri, United States

Location

Urology Cancer Center and GU Research Network

Omaha, Nebraska, United States

Location

Monter Cancer Center

Lake Success, New York, United States

Location

Columbia University Medical Center

New York, New York, United States

Location

Montefiore Medical Center, Albert Einstein College of Medicine

The Bronx, New York, United States

Location

Texas Oncology, P.A.

Dallas, Texas, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, United States

Location

Tom Baker Cancer Center

Calgary, Alberta, Canada

Location

Cross Cancer Center

Edmonton, Alberta, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health

Oshawa, Ontario, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

CHUM-Hospital Notre Dame

Montreal, Quebec, Canada

Location

Centre Hospitalier Régional et Universitaire - Hôpital

Bretonneau Tours, Centre-Val de Loire, France

Location

Institute Jean Godinot

Reims, Champagne-Ardenne, France

Location

Centre Hospitalier Universitaire de Rouen

Rouen, Haute-Normandie, France

Location

Centre Paul Papin

Angers, Pays de la Loire Region, France

Location

Medicale Centre René Gauducheau

Saint-Herblain, Pays de la Loire Region, France

Location

Institut Paoli Calmettes

Marseille, Provence-Alpes-Côte d'Azur Region, France

Location

Centre Antoine Lacassagne

Nice, Provence-Alpes-Côte d'Azur Region, France

Location

Centre Hospitalier Universitaire, Institut Gustave Roussy

Villejuif, Île-de-France Region, France

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Location

Klinikum Rechts der Isar der Technischen Universität

München, Bavaria, Germany

Location

Johann-Wolfgang-Goethe-Universität Frankfurt

Frankfurt am Main, Hesse, Germany

Location

Medizinische Hochschule Hannover

Hanover, Niedeersachen, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, Saarland, Germany

Location

Universitätsklinikum Dresden

Dresden, Saxony, Germany

Location

Universitätsklinikum Magdeburg A.ö.R.

Magdeburg, Saxony-Anhalt, Germany

Location

Universitätsklinikum Jena

Jena, Thuringia, Germany

Location

Universitätsklinikum Mainz

Mainz, Germany

Location

Azienda Ospedaliero-Universitaria Policlinico di Modena

Modena, Italy

Location

Fondazione IRCCS Policlinico San Matteo Pavia

Pavia, Italy

Location

Unità Operativa di Oncologia Medica

Roma, Italy

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Location

Akademicki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, Poland

Location

NZOZ Europejskie Centrum Zdrowia Otwock

Otwock, Masovian Voivodeship, Poland

Location

Centrum Onkologii Instytut im. M. Sklodowskiej-Curie

Warsaw, Masovian Voivodeship, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, Poland

Location

Zaklad Opieki Zdrowotnej MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, Warminski-Mazurskie, Poland

Location

Hospital Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

Location

Hospital Clinic I Provincial de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Vall d´Hebrón

Barcelona, Spain

Location

Institut Català D'Oncologia, Hospital Duran i Reynals

Madrid, Spain

Location

Instituto Valenciano de Oncología-Fundación (IVO-FINCIVO)

Valencia, Spain

Location

MeSH Terms

Conditions

Urologic Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

apatorsen; Gemcitabine; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Urinary Bladder Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Daniel Petrylak, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: October 18, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: October 7, 2016

Record last verified: 2016-10

Locations

CA (7); DE (9); IT (3); PL (6); ES (8); US (14); FR (8)