Study of Nab-Paclitaxel and Gemcitabine With or Without SBP-101 in Pancreatic Cancer

Study Overview
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Brief Summary
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The study is a randomized, double-blind, placebo-controlled, multicenter study of standard treatment with nab-paclitaxel and gemcitabine with or without SBP-101 in subjects previously untreated for metastatic pancreatic ductal adenocarcinoma (PDA), including subjects who have received prior neoadjuvant or adjuvant treatment.

Detailed Description
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The study will start with a 150-subject sentinel cohort and may continue with an expansion cohort depending on the results of a futility analysis to be performed when 104 required PFS events (death or disease progression, whichever comes first) are observed in the sentinel cohort.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study of Nab-Paclitaxel and Gemcitabine With or Without SBP-101 in Subjects Previously Untreated for Metastatic Pancreatic Ductal Adenocarcinoma

Conditions
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Pancreatic Cancer Metastatic, Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer Stage IV

Intervention / Treatment
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* Drug: SBP-101
* Drug: Nab-paclitaxel
* Drug: Gemcitabine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. Subjects with pancreatic acinar cell carcinoma may also be included. Is previously untreated for metastatic pancreatic ductal adenocarcinoma; metastatic disease must have been diagnosed within the past 3 months; and subject is expected to receive standard treatment with gemcitabine and nab-paclitaxel. Subjects who have had planned or prior surgery, such as a Whipple procedure, with or without neo-adjuvant/adjuvant chemotherapy may be included. Life expectancy ≥ 3 months. Measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan by RECIST v1.1 criteria. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. Adult, age ≥ 18 years, male or female. Females of child-bearing potential must have a negative serum pregnancy test within 14 days prior to start of study treatment and must use an adequate method of contraception during the study. All sexually active males must also use an adequate method of contraception during the study. Female subjects are considered to be of childbearing potential unless they are postmenopausal (at least 12 months of consecutive amenorrhea, without other known or suspected cause) and over 55 years old or have been sterilized surgically (i.e., bilateral tubal ligation, hysterectomy or bilateral oophorectomy, all with surgery at least one month before dosing). Adequate bone marrow, hepatic and renal function as outlined in protocol. Corrected QT interval (QTc); QTc interval ≤ 470 msec at Baseline. Willing and able to provide written informed consent: voluntary agreement to participate in the study following disclosure of risks and procedures required. Exclusion Criteria: Subjects known to be BRCA (BReast CAncer gene antigen) positive. Subjects taking metformin. Diabetic subjects on treatment with metformin, or any other derivative thereof, must discontinue it while on study (other diabetic medications are allowed). History of retinopathy or macular degeneration. Evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the Investigator or Medical Monitor, makes it undesirable for the subject to participate in the study or that would jeopardize compliance with the protocol. Subjects with pre-existing well-controlled diabetes are not excluded. Medical or psychiatric conditions that compromise the subject's ability to give informed consent or to complete the protocol or a history of non-compliance. Presence of islet-cell or pancreatic neuroendocrine tumor or mixed adenocarcinoma-neuroendocrine carcinoma. Symptomatic central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required. Serum albumin < 30 g/L (3.0 g/dL). Occurrence of deep vein thrombosis (DVT) or portal vein occlusion, pulmonary embolism (PE), or other thromboembolic event during screening. Presence of known active bacterial, fungal, or viral infection requiring systemic therapy. Known active infection with human immunodeficiency virus (HIV), hepatitis B or C. Presence of interstitial lung disease, pulmonary fibrosis, or pulmonary hypersensitivity reaction. Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV. Pregnant or lactating. Major surgery within 4 weeks of the start of study treatment, without complete recovery. Known hypersensitivity to any component of study treatments. Participation in any other clinical investigation within 4 weeks of receiving the first dose of study drug. Any history of hydroxychloroquine use (Plaquenil® and other brand names).

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
Interventional Model Description: 1:1 randomization to Experimental Arm vs. Control Arm
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>SBP-101 + Nab-paclitaxel and Gemcitabine | Drug: SBP-101<br>* small molecule polyamine metabolic inhibitor for subcutaneous injection<br>* Other names: diethyl dihydroxyhomospermine;Drug: Nab-paclitaxel<br>* paclitaxel protein-bound particles for injectable suspension<br>* Other names: Abraxane;Drug: Gemcitabine<br>* gemcitabine for injection<br>* Other names: Gemzar;|
| Placebo Comparator: Control Arm<br>Placebo + Nab-Paclitaxel and Gemcitabine | Drug: Nab-paclitaxel<br>* paclitaxel protein-bound particles for injectable suspension<br>* Other names: Abraxane;Drug: Gemcitabine<br>* gemcitabine for injection<br>* Other names: Gemzar;Other: Placebo<br>* Normal Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Compare OS between subjects who receive SBP-101 and those who do not receive SBP-101 (i.e., placebo) in combination with nab-paclitaxel and gemcitabine | Randomization (Day 1) until death from any cause assessed up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Compare PFS between SBP-101 and placebo | Randomization (Day 1) until disease progression or death from any cause, whichever occurs first, assessed up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SBP-101