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

NCT ID: NCT01454089

Last Updated: 2016-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 183 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2014-11-30

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 All participants have an End of Treatment (EOT) visit when they are withdrawn from all study treatment (chemotherapy and maintenance).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

Conditions

Urologic Neoplasms; Metastatic Bladder Cancer; Urinary Tract Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

OGX-427 600 mg

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

Group Type: EXPERIMENTAL

OGX-427 600 mg

Intervention Type: 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.

Gemcitabine

Intervention Type: 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.

Cisplatin

Intervention Type: 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.

Carboplatin

Intervention Type: 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

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

Group Type: EXPERIMENTAL

OGX-427 1000 mg

Intervention Type: 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.

Gemcitabine

Intervention Type: 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.

Cisplatin

Intervention Type: 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.

Carboplatin

Intervention Type: 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.

Placebo

Standard chemotherapy (gemcitabine and cisplatin) in combination with placebo

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: 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.

Gemcitabine

Intervention Type: 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.

Cisplatin

Intervention Type: 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.

Carboplatin

Intervention Type: 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.

Interventions

OGX-427 600 mg

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.

Intervention Type: DRUG

OGX-427 1000 mg

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Gemcitabine

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.

Intervention Type: DRUG

Cisplatin

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.

Intervention Type: DRUG

Carboplatin

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.

Intervention Type: DRUG

Other Intervention Names

apatorsen; apatorsen

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

Achieve Life Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Petrylak, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

City of Hope National Medical Center

Duarte, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of California Los Angeles

Los Angeles, California, United States

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Radiological Associates of Sacramento

Sacramento, California, United States

Yale University

New Haven, Connecticut, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Siteman Cancer Center, Washington University School of Medicine

St Louis, Missouri, United States

Urology Cancer Center and GU Research Network

Omaha, Nebraska, United States

Monter Cancer Center

Lake Success, New York, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Medical Center, Albert Einstein College of Medicine

The Bronx, New York, United States

Texas Oncology, P.A.

Dallas, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Tom Baker Cancer Center

Calgary, Alberta, Canada

Cross Cancer Center

Edmonton, Alberta, Canada

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

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

Oshawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

CHUM-Hospital Notre Dame

Montreal, Quebec, Canada

Centre Hospitalier Régional et Universitaire - Hôpital

Bretonneau Tours, Centre-Val de Loire, France

Institute Jean Godinot

Reims, Champagne-Ardenne, France

Centre Hospitalier Universitaire de Rouen

Rouen, Haute-Normandie, France

Centre Paul Papin

Angers, Pays de la Loire Region, France

Medicale Centre René Gauducheau

Saint-Herblain, Pays de la Loire Region, France

Institut Paoli Calmettes

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

Centre Antoine Lacassagne

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

Centre Hospitalier Universitaire, Institut Gustave Roussy

Villejuif, Île-de-France Region, France

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Klinikum Rechts der Isar der Technischen Universität

München, Bavaria, Germany

Johann-Wolfgang-Goethe-Universität Frankfurt

Frankfurt am Main, Hesse, Germany

Medizinische Hochschule Hannover

Hanover, Niedeersachen, Germany

Universitätsklinikum des Saarlandes

Homburg, Saarland, Germany

Universitätsklinikum Dresden

Dresden, Saxony, Germany

Universitätsklinikum Magdeburg A.ö.R.

Magdeburg, Saxony-Anhalt, Germany

Universitätsklinikum Jena

Jena, Thuringia, Germany

Universitätsklinikum Mainz

Mainz, , Germany

Azienda Ospedaliero-Universitaria Policlinico di Modena

Modena, , Italy

Fondazione IRCCS Policlinico San Matteo Pavia

Pavia, , Italy

Unità Operativa di Oncologia Medica

Roma, , Italy

Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

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

Wroclaw, Lower Silesian Voivodeship, Poland

NZOZ Europejskie Centrum Zdrowia Otwock

Otwock, Masovian Voivodeship, Poland

Centrum Onkologii Instytut im. M. Sklodowskiej-Curie

Warsaw, Masovian Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, Poland

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

Olsztyn, Warminski-Mazurskie, Poland

Hospital Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

Hospital Clinic I Provincial de Barcelona

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Vall d´Hebrón

Barcelona, , Spain

Institut Català D'Oncologia, Hospital Duran i Reynals

Madrid, , Spain

Instituto Valenciano de Oncología-Fundación (IVO-FINCIVO)

Valencia, , Spain

Countries

United States; Canada; France; Germany; Italy; Poland; Spain

Other Identifiers

OGX-427-02

Identifier Type: -

Identifier Source: org_study_id