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

Urologic Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01454089
• Other study ID #: OGX-427-02
• Status: Completed
• Phase: Phase 2
• First received: October 5, 2011
• Last updated: October 6, 2016
• Start date: October 2011
• Est. completion date: November 2014

Study information

• Verified date: October 2016
• Source: OncoGenex Technologies
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines AgencyCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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 All participants have an End of Treatment (EOT) visit when they are withdrawn from all study treatment (chemotherapy and maintenance).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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 183
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Metastatic Bladder Cancer
• Neoplasms
• Urinary Bladder Neoplasms
• Urinary Tract Neoplasms
• Urologic Neoplasms

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Cross Cancer Center	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	CHUM-Hospital Notre Dame	Montreal	Quebec
Canada	R. S. McLaughlin Durham Regional Cancer Center at Lakeridge Health	Oshawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
France	Centre Paul Papin	Angers Cedex 9	Pays De La Loire
France	Centre Hospitalier Régional et Universitaire - Hôpital	Bretonneau Tours	Centre
France	Institut Paoli Calmettes	Marseille Cedex 9	Provence Alpes Cote D'Azur
France	Centre Antoine Lacassagne	Nice	Provence Alpes Cote d'Azur
France	Institute Jean Godinot	Reims	Champagne-Ardenne
France	Centre Hospitalier Universitaire de Rouen	Rouen	Haute-Normandie
France	Medicale Centre René Gauducheau	St. Herblain Cedex	Pays de la Loire
France	Centre Hospitalier Universitaire, Institut Gustave Roussy	Villejuif Cedex	Ile-de-france
Germany	Universitätsklinikum Dresden	Dresden	Sachsen
Germany	Johann-Wolfgang-Goethe-Universität Frankfurt	Frankfurt	Hessen
Germany	Medizinische Hochschule Hannover	Hannover	Niedeersachen
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Wuerttemberg
Germany	Universitätsklinikum des Saarlandes	Homburg	Saarland
Germany	Universitätsklinikum Jena	Jena	Thuringen
Germany	Universitätsklinikum Magdeburg A.ö.R.	Magdeburg	Sachsen-Anhalt
Germany	Universitätsklinikum Mainz	Mainz
Germany	Klinikum Rechts der Isar der Technischen Universität	München	Bayern
Italy	Azienda Ospedaliero-Universitaria Policlinico di Modena	Modena
Italy	Fondazione IRCCS Policlinico San Matteo Pavia	Pavia
Italy	Unità Operativa di Oncologia Medica	Roma
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka w Bydgoszczy	Bydgoszcz	Kujawsko-Pomorskie
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Zaklad Opieki Zdrowotnej MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn	Warminski-Mazurskie
Poland	NZOZ Europejskie Centrum Zdrowia Otwock	Otwock	Mazowieckie
Poland	Centrum Onkologii Instytut im. M. Sklodowskiej-Curie	Warszawa	Mazowieckie
Poland	Akademicki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d´Hebrón	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Institut Català D'Oncologia, Hospital Duran i Reynals	Madrid
Spain	Instituto Valenciano de Oncología-Fundación (IVO-FINCIVO)	Valencia
United States	Montefiore Medical Center, Albert Einstein College of Medicine	Bronx	New York
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Monter Cancer Center	Lake Success	New York
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	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Urology Cancer Center and GU Research Network	Omaha	Nebraska
United States	Radiological Associates of Sacramento	Sacramento	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Siteman Cancer Center, Washington University School of Medicine	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
OncoGenex Technologies	PRA Health Sciences

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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.	From initiation of study drug to end of study (up to 8 months)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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.	Baseline to measured progressive disease (up to approximately 12 months)	No
Secondary	Overall Response Rate (ORR) and Disease Control Rate	Participants were defined as having an "overall response" if their best response is either confirmed CR, confirmed PR, unconfirmed CR or unconfirmed PR. ORR was defined as the percent of participants who had an overall response. Participants were defined as having "disease control" if their best response is confirmed CR, confirmed PR, unconfirmed CR, unconfirmed PR or SD. The disease control rate (DCR) was defined as the percent of participants with disease control. (See "Best Objective Tumor Response" Outcome Measure above for response category definitions.)	Baseline to measured progressive disease (up to approximately 12 months)	No
Secondary	Duration of Overall Response Rate	Overall response was defined has having a response of Complete Response (CR) or Partial Response (PR). (See "Best Objective Tumor Response" Outcome Measure above for response category definitions.) Duration of Response is defined as the duration from the first overall response to the first Stable Disease (SD) or Disease Progression (PD), whichever happens first. If no SD or PD, subject is censored at the last tumor assessment (prior to other anti-cancer therapy if applicable).	Baseline to measured progressive disease (up to approximately 12 months)	No
Secondary	Progression-free Survival (PFS)	PFS was defined as the time from randomization to the date of disease progression or death, whichever occurred first, before or after treatment discontinuation. For participants still on study and those who remained alive and had not progressed after treatment discontinuation, PFS was censored on the date of the last tumor assessment.	Baseline to measured progressive disease (up to approximately 12 months)	No
Secondary	Change From Baseline in Serum Hsp27 levels by End of Treatment	End of Treatment is last non-hemolyzed observation up to last dose + 30 days. Includes unscheduled and additional treatment visits. Hemolyzed samples were excluded.	Baseline, End of Treatment (up to approximately 12 months)	No
Secondary	Change From Baseline in Serum Clusterin Levels by End of Treatment	End of Treatment is last observation up to last dose + 30 days. Includes unscheduled and additional treatment visits.	Baseline, End of Treatment (up to approximately 12 months)	No
Secondary	Change From Baseline in Circulating Tumor Cell (CTC) Count by End of Treatment	End of Treatment is last observation up to last dose + 30 days. Includes unscheduled and additional treatment visits.	Baseline, End of Treatment (up to approximately 12 months)	No
Secondary	Serum OGX-427 Cmax and Trough Levels	only C1 to C6, Ctrough and Cmax - as well report EOT Ctrough	Cycle 1 Day 1 through Cycle 6 Day 1, End of Treatment (up to approximately 12 months)	No