Detailed Description:
This trial will enroll approximately 600 patients to evaluate the effect of SBP-101 on
Overall Survival when administered with gemcitabine and nab-paclitaxel compared to
gemcitabine and nab-paclitaxel and a placebo. Secondary endpoints include Progression-free
survival, radiologic responses to treatment, and Quality of Life measures. An independent,
external Data Safety Monitoring Board (DSMB) will monitor safety and efficacy and a planned
futility analysis.
Inclusion Criteria:
- Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma.
- 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/or
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 from 2 weeks before the first administration of SBP-101 until 6 months
after the last administration of study drug (i.e., last dose of any of the three drugs
in the regimen). 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.
- QTc interval ≤ 470 ms (for women) and ≤ 450 ms (for men) on the ECG at baseline
calculated by either the Fridericia or Framingham formula.
- Willing and able to provide written informed consent: voluntary agreement to
participate in the study following disclosure of risks and procedures required.
Exclusion Criteria:
- When results of germline or somatic testing done prior to screening are known,
subjects known to have mutations of the BRCA 1/2 (Breast Cancer gene) are excluded.
- Concomitant metformin administration. Diabetic subjects on treatment with metformin,
or any other derivative thereof, must discontinue it at least 5 days prior to C1D1 and
not take metformin while on study (other diabetic medications are allowed).
- Any history of retinopathy or at risk for retinal detachment (personal or family
history of retinal detachment, extreme myopia [-6.0 diopters or approximately 20/500],
eye surgery <6 months prior to C1D1, or history of a severe eye injury. Subjects with
findings of retinopathy on baseline ophthalmology exams will be excluded.
- 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).
- Deep vein thrombosis (DVT) or portal vein occlusion, pulmonary embolism (PE), or other
thromboembolic event that occurs 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 prior to the start of study drug 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).
Primary outcome:
1. Overall Survival (OS) (Time Frame - From date of first dose up to 100 weeks or until death):
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
Secondary outcome:
1. Progression Free Survival (PFS) (Time Frame - From date of first dose up to 100 weeks or until death):
Compare PFS between SBP-101 and placebo
- Experimental: Experimental Arm
SBP-101 + Nab-paclitaxel and Gemcitabine - Placebo Comparator: Control Arm
Placebo + Nab-Paclitaxel and Gemcitabine
- SBP-101 (ivospemin):
small molecule polyamine metabolic inhibitor for subcutaneous injection - Nab-paclitaxel (Abraxane):
paclitaxel protein-bound particles for injectable suspension - Gemcitabine (Gemzar):
gemcitabine for injection - Placebo:
Normal Saline
Quelle: ClinicalTrials.gov
