Phase II Trial Of Gemcitabine Plus Nab-Paclitaxel +/- OGX-427 In Patients With Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare the overall survival in patients with previously untreated metastatic pancreatic cancer receiving gemcitabine/nab-paclitaxel plus OGX-427 or gemcitabine/nab-paclitaxel plus placebo.

Detailed Description
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Patients with pancreatic cancer usually present with inoperable disease and systemic therapy becomes the primary form of treatment. The combination of gemcitabine plus nab-paclitaxel represents an appropriate front-line standard of care for patients with metastatic pancreatic cancer. However, poor outcomes with this disease warrant exploration of novel drugs with unique mechanisms of action. Preclinical evidence suggests that OGX-427 has shown promising activity in pancreatic cancer. In this trial, we will compare the overall survival of patients with previously untreated metastatic pancreatic cancer using OGX-427 with either gemcitabine/nab-paclitaxel or a placebo with gemcitabine/nab-paclitaxel.

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled Phase II Trial Of Gemcitabine Plus Nab-Paclitaxel Combined With OGX-427 Or Placebo In Patients With Metastatic Pancreatic Cancer (The Rainier Trial)

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: OGX-427
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically- or cytologically confirmed pancreatic adenocarcinoma Stage IV disease (measurable disease NOT required) Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 At least 18 years of age Female patients who are not of child-bearing potential, and fertile female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of randomization. Fertile male patients willing to use adequate contraceptive measures. Adequate bone marrow, renal, and hepatic function. Ability to understand the nature of this study protocol, comply with study and/or follow-up procedures, and give written informed consent Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: Any prior systemic or investigational therapy for metastatic pancreatic cancer. Systemic therapy administered alone or in combination with radiation in the adjuvant or neoadjuvant setting is permissible as long as it was completed > 6 months prior to the time of study randomization. History of other diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that, in the opinion of the investigator, renders the subject at high risk from treatment complications or might affect the interpretation of the results of the study. Presence of known central nervous system or brain metastases. Known human immunodeficiency virus (HIV) infection. Active second invasive malignancy (except non-melanomatous skin cancer), defined as any malignancy with current need for cancer therapy or high possibility (>30%) of recurrence during the study. Patients receiving warfarin. However, therapeutic anticoagulation with Low Molecular Weight Heparin (LMWH) is allowed. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease, and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months. Current sensory neuropathy > Grade 1. Major surgery within 4 weeks of the start of study treatment (defined as those surgeries that require general anesthesia. Insertion of a vascular access device is NOT considered major surgery.). Patients must have recovered from the side effects of any major surgery prior to randomization.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OGX-427<br>Three loading doses of OGX-427 at 600mg IV will be administered Days -9 to -1. Following the loading dose period, OGX-427 will be administered at 600mg IV weekly Days 1, 8, 15, and 22 of each 28 day cycle during the Treatment Phase. | Drug: OGX-427<br>* Three separate administrations of OGX-427 will be given during the 9-day Loading Dose Period. Following the Loading Dose Period, patients will receive 600mg OGX-427 prior to the administration of nab-paclitaxel (125mg/m2 IV)and gemcitabine (1000mg/m2 IV)administration on Day 1, 8, and 15 of each cycle. OGX-427 will also be administered on Day 22 during each cycle (i.e., weekly). Patients will continue 28 day treatment cycles until disease progression or until other reasons for discontinuation from treatment.<br>|
| Placebo Comparator: Placebo<br>Three loading doses of placebo will be administered Days -9 to -1. Following the loading dose period, placebo will be administered weekly Days 1, 8, 15, and 22 of each 28 day cycle. | Drug: Placebo<br>* Three separate administrations of Placebo will be given during the 9-day Loading Dose Period. Following the Loading Dose Period, patients will receive placebo prior to the administration of nab-paclitaxel (125mg/m2 IV)and gemcitabine (1000mg/m2 IV)administration on Day 1, 8, and 15 of each cycle. Placebo will also be administered on Day 22 during each cycle (i.e., weekly). Patients will continue 28 day treatment cycles until disease progression or until other reasons for discontinuation from treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival defined as the time, in months, from date of randomization until date of death or date last known alive whichever comes first, assessed up to 2 years. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | The time (in months) that patients are progression-free, assessed from date of randomization to date of first documented disease progression or date of death from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest (nadir) sum while on study (this includes the baseline sum if that is the smallest on study), or the appearance of one or more new lesions. | Every 8 weeks up to 2 years | 
| Objective Response Rate | Objective response rate defined as the percent of patients having a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR=complete disappearance of all target lesions. PR=decrease in baseline of 30% or more of the diameter(s) of all target lesions. | Every 8 weeks for up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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untreated, metastatic, OGX-427