Metastatic Pancreatic Ductal Adenocarcinoma
Conditions
Sponsors
Panbela Therapeutics, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject must meet all of the following inclusion criteria to be eligible for enrollment in this study: 1. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma. Subjects with pancreatic acinar cell carcinoma may also be included. 2. 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. 3. Life expectancy =3 months. 4. Measurable disease on CT or MRI scan by RECIST v 1.1 criteria. 5. ECOG Performance Status 0-1. 6. Adult, age = 18 years, male or female. 7. 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). 8. Adequate bone marrow, hepatic, renal, and coagulation function as defined by the following: a. Absolute neutrophil count =1.5 x 109/L b. Hemoglobin =9.0 g/dL (90 g/L) c. Platelets =100 x 109/L d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x upper limit of normal (ULN) (if no hepatic metastases). If hepatic tumor involvement, AST and ALT =5 x ULN. e. Bilirubin =1.5 x ULN f. Calculated creatinine clearance >50 mL/min using the Cockcroft and Gault equation 9. QTc interval = 470 msec at Baseline. 10. Willing and able to provide written informed consent: voluntary agreement to participate in the study following disclosure of risks and procedures required. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: Subjects are excluded from this study if any of the following conditions are met: 1. Subjects known to be BRCA positive. 2. 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). 3. History of retinopathy or macular degeneration. 4. 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. 5. 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. 6. Presence of islet-cell or pancreatic neuroendocrine tumor or mixed adenocarcinoma-neuroendocrine carcinoma. 7. Symptomatic CNS malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required. 8. Serum albumin <30 g/L (3.0 g/dL). 9. Occurrence of deep vein thrombosis (DVT) or portal vein occlusion, pulmonary embolism (PE), or other thromboembolic event during screening. 10. Presence of known active bacterial, fungal, or viral infection requiring systemic therapy. 11. Known active infection with human immunodeficiency virus (HIV), hepatitis B or C. 12. Presence of interstitial lung disease, pulmonary fibrosis, or pulmonary hypersensitivity reaction. 13. Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV. 14. Pregnant or lactating. 15. Major surgery within 4 weeks of the start of study treatment, without complete recovery. 16. Known hypersensitivity to any component of study treatments. 17. Participation in any other clinical investigation within 4 weeks of receiving the first dose of study drug. 18. Any history of hydroxychloroquine use (Plaquenil® and other brand names).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare overall survival (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 Objective: The secondary objective is to compare progression free survival (PFS) between SBP-101 and placebo. Other Secondary Efficacy: To compare overall objective response (ORR) between SBP-101 and placebo To compare disease control rate (DCR) between SBP-101 and placebo To compare duration of response (DoR) between SBP-101 and placebo To compare changes in quality of life (QOL) scores between SBP-101 and placebo To compare the safety and tolerability of SBP-101 compared to placebo when administered in combination with nab-paclitaxel and gemcitabine. Exploratory: To compare the effects of SBP-101 and placebo on blood levels of CA19-9 and circulating tumor DNA (cT DNA).;Primary end point(s): OS defined as the time from randomization (Day 1) The primary efficacy endpoint, OS, and secondary efficacy endpoints of PFS and DoR will be evaluated using log-rank test; hazard ratios (placebo/SBP-101) and 2-sided 90% confidence intervals will be estimated. The difference between treatment groups in ORR will be evaluated using exact test along with 2-sided 90% confidence intervals. The difference in DCR between SBP-101 and placebo will be assessed using the Cochran-Mantel-Haenszel general association test.;Timepoint(s) of evaluation of this end point: OS is defined as the time from randomization (Day 1) until death from any cause (up to 2 years). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS defined as the time from randomization (Day 1) until disease progression or death from any cause, whichever occurs first. ORR defined as the percentage of subjects with a best overall response of CR or PR, as determined by independent, central assessment using RECIST 1.1 criteria DCR defined as the percentage of subjects who have a best overall response of CR, PR, or SD for at least 16 weeks. DoR in subjects who achieve a CR or PR, defined as time from onset of CR or PR until disease progression. This variable is undefined for subjects who do not achieve a CR or PR. QOL assessed using EORTC QLQ-30 and QLQ-PAN26 questionnaires. Treatment emergent adverse events (TEAEs) • Clinically important changes in safety laboratory tests and vital signs. • Changes in response to a vision-centered questionnaire and serial ophthalmologic examinations. Exploratory: • Proportion of subjects with any CA19-9 decrease from baseline, CA19-9 decrease at Week 8, and maximum CA19-9 decrease =60%. • Blood levels of cT DNA biomarkers;Timepoint(s) of evaluation of this end point: See 5.1.1 | — |
Countries
Australia, Austria, Belgium, France, Germany, Italy, Korea, Republic of, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactMichael Walker, MD
Panbela Therapeutics, Inc
Outcome results
None listed