An Efficacy Study of MORAb-009 in Subjects With Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to investigate the activity of MORAb-009 when added to a standard regimen of gemcitabine in patients with previously untreated unresectable stage 3 or 4 pancreatic cancer.

Official Title
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A Phase 2 Randomized, Placebo-controlled, Double-blind Study of the Efficacy of MORAb-009 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer.

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: MORAb-009
* Drug: Placebo
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male subjects, ≥ 18 years of age, with cytologically or histologically confirmed diagnosis of pancreatic adenocarcinoma. Must have measurable disease, as defined by RECIST or evaluable by clinical signs/symptoms (e.g. ascites, pleural effusion, or lesions of less than 2 cm) supported by biomarker, radiologic, or pathologic studies conducted within 4 weeks prior to study entry. Must have unresectable disease and have received no prior chemotherapy or radiation therapy for their pancreatic cancer. Karnofsky performance status of greater than or equal to 70 %. Female subjects of childbearing potential and all male subjects must be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period. Other significant medical conditions must be well-controlled and stable in the opinion of the investigator for at least 30 days prior to Study Day 1. Laboratory and clinical results within the 2 weeks prior to Study Day 1 as follows: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL Serum bilirubin ≤ 2.0 mg/dL Aspartate transaminase (AST)* ≤ 5 x upper limit of normal (ULN) Alanine transaminase (ALT)* ≤ 5 x ULN Alkaline phosphatase* ≤ 5 x ULN Serum creatinine ≤ 2.0 mg/dL Stenting to reduce liver functions to qualifying levels is permitted. * Subjects with liver function abnormalities greater than the ULN are eligible only if in the opinion of the investigator they are due to disease obstruction of the bile ducts or metastatic disease. Must be willing and able to provide written informed consent. Exclusion Criteria: Known central nervous system (CNS) tumor involvement. Evidence of other active malignancy requiring treatment. Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4 angina not well controlled by medication, or myocardial infarction within 6 months). Electrocardiogram (ECG) demonstrating clinically significant arrhythmias (Note: Subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia [SVT], are eligible). Active serious systemic disease, including active bacterial or fungal infection. Active viral hepatitis or symptomatic human immunodeficiency virus (HIV) infection. Prior chemotherapy or radiation therapy for their pancreatic cancer. Breast-feeding, pregnant, or likely to become pregnant during the study. No other concurrent immunotherapy (e.g., immunosuppressants or chronic use of systemic corticosteroids with the exception that low-dose corticosteroids are allowed) Known hypersensitivity to a monoclonal antibody or biologic therapy.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MORAb-009<br>MORAb-009 plus gemcitabine ('MORAb-009'): MORAb-009 was administered at 5 mg/kg on Day 1 of Weeks 1 through 7 during the first cycle and on Day 1 of Weeks 1 through 3 of subsequent cycles. Gemcitabine was administered by i.v. infusion at an initial dose of 1000 mg/m2 once weekly for up to 7 weeks (or until toxicity necessitated reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles consisted of infusions once weekly for 3 consecutive weeks, followed by a week of rest from treatment. | Drug: MORAb-009<br>* Monoclonal antibody administered once weekly by intravenous injection.<br>Drug: Gemcitabine<br>* Gemcitabine was administered by i.v. infusion at an initial dose of 1000 mg/m2 once weekly for up to 7 weeks (or until toxicity necessitated reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles consisted of infusions once weekly for 3 consecutive weeks, followed by a week of rest from treatment.<br>|
| Active Comparator: Placebo<br>Placebo plus gemcitabine ('Placebo') Placebo was administered on Day 1 of Weeks 1 through 7 during the first cycle and on Day 1 of Weeks 1 through 3 of subsequent cycles. Gemcitabine was administered by i.v. infusion at an initial dose of 1000 mg/m2 once weekly for up to 7 weeks (or until toxicity necessitated reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles consisted of infusions once weekly for 3 consecutive weeks, followed by a week of rest from treatment. | Drug: Placebo<br>* As per package insert.<br>Drug: Gemcitabine<br>* Gemcitabine was administered by i.v. infusion at an initial dose of 1000 mg/m2 once weekly for up to 7 weeks (or until toxicity necessitated reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles consisted of infusions once weekly for 3 consecutive weeks, followed by a week of rest from treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | This measure was defined as the time (in months) from the date of randomization to the date of death, whatever the cause. The primary endpoint was analyzed when 110 events (deaths) were observed. In the absence of death confirmation or for subjects alive at the time of analysis, the survival time will be censored at the date of the last study follow-up. | 1-21 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free Survival (PFS) is defined as the time from the date of randomization to the date of the first observation of disease progression (clinical or radiological) or death due to any cause. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline. If progression or death is not observed, the PFS time will be censored at the date of the last tumor assessment without evidence of progression prior to the date of initiation of further anticancer treatment. | 1-21 Months | 
| Best Overall Response Rate | Best overall response is the number of participants with a Complete Response (CR) or Partial Response (PR), as classified by independent blinded review of the CT or MRI images, based on RECIST 1.0. A CR is the disappearance of all target lesions. PR is at least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum longest diameter. Progressive Disease (PD) is at least a 20% increase in the sum of the longest diameters of target lesions or the appearance of one or more new lesions. Stable disease (SD) is neither CR, PR or PD. | Baseline to response up to 21 months |