E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Pancreatic Ductal Adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective is to compare progression free survival (PFS) between SBP-101 and placebo.
Other Secondary Efficacy: To compare objective response rate (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 (cTDNA). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. 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 from 2 weeks before the first administration of SBP-until 6 months after the last administration of the 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). Male subjects with partners who are oCBP should also use a highly effective contraceptive measure during the study and through 6 months following the last administration of study drug. Male subjects are considered of reproductive potential following puberty, unless permanently sterilized by bilateral vasectomy. Male subjects oCBP should be counseled to consider cryogenic preservation of sperm prior to study initiation due to the possibility of infertility post-treatment. 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 using the Cockcroft and Gault equation >50 mL/min 9. QTc interval of ≤ 470 ms (for women) and ≤ 450 ms (for men) on the ECG baseline calculated by either the Fridericia or Framingham formula. 10. Willing and able to provide written informed consent: voluntary agreement to participate in the study following disclosure of risks and procedures is required. |
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E.4 | Principal exclusion criteria |
Subjects are excluded from this study if any of the following conditions are met: 1. When results of germline or somatic testing done prior to screening are known, subjects known to have mutations of the BRCA1/2 (Breast are known, subjects known to have mutations of the BRCA1/2 (Breast Cancer gene). If not done previously as standard of care, testing for mutated BRCA 1/ 2 genes may be initiated at the discretion of the site Investigator, and in parallel, screening and treatment may proceed before the results are known. 2. 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). 3. 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. 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. Deep vein thrombosis (DVT) or portal vein occlusion, pulmonary embolism (PE), or other thromboembolic event that occurs during screening. Subjects with events that occurred prior to screening and are on stable therapy are not excluded. 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 drug treatments. 17. Participation in any other clinical investigation within 4 weeks of receiving the first dose of study drug. Participation in observational trials is not excluded. 18. Any history of hydroxychloroquine use (Plaquenil® and other brand names) within the last 12 months prior to dosing of SBP-101. |
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E.5 End points |
E.5.1 | Primary end point(s) |
OS defined as the time (days) from Study Day 1 (the date of first dose of study drug treatment) until death from any cause. 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. |
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E.5.1.1 | 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). |
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E.5.2 | Secondary end point(s) |
PFS defined as the time (days) from Study 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 confirmed CR, confirmed PR, or SD for at least 16 weeks. DoR in subjects who achieve a CR or PR, defined as time from onset of first response (CR or PR) until disease progression or death from any cause, whichever occurs first. This endpoint is undefined for subjects who do not achieve a CR or PR. QOL assessed using EORTC QLQ-30 and QLQ-PAN26 questionnaires. 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 cTDNA biomarkers. Note all ctDNA collection will be halted at interim analysis.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 69 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Korea, Republic of |
United Kingdom |
United States |
Austria |
Belgium |
France |
Germany |
Italy |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Unless the trial enrollment is stopped for futility after the interim futility analysis, the study is completed when the required total of 512 OS events have been observed, hence, study duration is driven by the occurrence of the pre-specified number of OS events. All enrolled subjects will be followed for OS until the end of study or death, whichever occurs first.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |