A Randomized Study of Amplimexon (Imexon) With Gemcitabine in Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine if imexon in combination with gemcitabine could improve overall survival as compared to gemcitabine alone in subjects with pancreatic cancer that has spread to other organs such as the liver or lungs. The study will also look at the safety of the combination as compared to gemcitabine alone. Participants in the study will be randomly assigned to either treatment and neither the participant or their doctors will know which treatment they will be receiving.

Official Title
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A Phase 2 Randomized, Double-Blind, Multicenter Trial of Amplimexon® Plus Gemcitabine Versus Gemcitabine Plus Placebo in Patients With Metastatic Chemotherapy Naïve Pancreatic Adenocarcinoma (Stage IV)

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Drug: imexon in combination with gemcitabine
* Drug: imexon placebo + gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically confirmed, chemotherapy naive, metastatic pancreatic adenocarcinoma (Stage IV). This does not include patients with only locally advanced pancreatic cancer. At least one unidimensional measurable metastatic lesion by contrast enhanced CT scan (or MRI in patients ineligible for contrast enhanced CT) that are outside any prior radiation port. Age at least 18 years. ECOG performance status 0 or 1. No prior chemotherapy or radiation therapy. Projected life expectancy at least 2 months. If female, neither pregnant nor lactating. If of child bearing potential must agree to, and be able to use adequate contraception. Concomitant disease: No respiratory insufficiency requiring oxygen therapy; no angina at rest; no myocardial infarction in previous 3 months; no life threatening ventricular arrhythmias. No uncompensated CHF or NY Heart Association class 3 or 4 cardiac disease. No other concurrent active malignancy. No infection requiring parenteral antibiotic therapy at the start of protocol treatment. Laboratory values within the following criteria: Hgb greater than or equal to 9 gm/dL WBC greater than or equal 3,500/mm^3 ANC greater than or equal 1,500/mm^3 Platelet count greater than or equal 100,000/mm^3 Creatinine greater than or equal 2.0 Bilirubin less than or equal to 2.0 Hepatic enzymes (AST, ALT) less than or equal 3 times upper limit of normal (ULN) G6PD level greater than or equal lower limit of normal (LLN). Able to render informed consent and follow protocol requirements. Exclusion Criteria: Patients with locally advanced, non-metastatic pancreas cancer (Stage III or below). Age less than 18 years. ECOG performance status 2 or greater. Prior anticancer drug therapy for metastatic disease. Ascites. Prior abdominal or thoracic surgery < 4 weeks before the start of therapy. Current or prior brain metastases. Brain MRI or CT required pre-registration only if the patient has CNS symptoms indicating a need for evaluation. Life expectancy projected less than 2 months. Pregnancy or lactation. Unable or unwilling to utilize medically acceptable contraception if of childbearing potential. Laboratory parameters outside of specified ranges, (see above). Infection requiring parenteral antibiotics. NY Heart Association stage 3 or 4 heart disease. Unable to render informed consent. Failure to meet any of the eligibility criteria as outlined above.

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: imexon + gemcitabine<br>imexon + gemcitabine | Drug: imexon in combination with gemcitabine<br>* 875 mg/m^2 imexon IV + 1000 mg/m^2 gemcitabine IV<br>* Other names: Amplimexon, Gemzar;|
| Active Comparator: Placebo + gemcitabine<br>Placebo in combination with gemcitabine | Drug: imexon placebo + gemcitabine<br>* imexon placebo IV + 1000 mg/m^2 gemcitabine IV<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival for the Intent to Treat Population | To compare the overall survival duration of the two treatment arms. Overall survival is measured from the time of randomization until reported death. Subjects were censored at last time known alive if lost to follow-up. Alive patients were censored at the last survival follow-up. Follow-up was monthly after off study treatment. | up to 2 years | 
| To Evaluate and Compare the Tolerability and Toxicity of the Two Treatment Arms by Comparing Adverse Events | Number of Participants with Adverse Events were compared between the two arms to detect any differences in number or types of events | Adverse events were collected from the time of treatment until the participant went off study treatment, an average of 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rates of the Two Treatment Arms | Objective response is measured by tumor reduction as defined in the RECIST criteria. Tumor shrinkage must be at least 30% to qualify as an objective response. | one year | 
| Progression Free Survival | To compare the median progression free survival (PFS) of the two treatment arms. Progression free survival is measured from randomization until the subject has documented disease progression by an objective measure. Subjects were censored if no documented progression had occurred at the one year time point. Subjects must be alive with no more than 20% increase in tumor size to qualify for progression free survival. Changes in tumor size are defined by RECIST criteria. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, metastatic, chemotherapy naive