None listed
Conditions
Brief summary
The main goal of this study is to assess the safety and tolerability of the drug SBP-101 in patients with pancreatic cancer. You may be eligible to join this study if you are aged 18 years or above and have been diagnosed with metastatic or locally advanced ductal adenocarcinoma of the pancreas, which has been previously treated with chemotherapy. Study details: Participants in the first part of this study (Phase 1a) will be administered SBP-101 in a dose-escalation scheme with cohorts at each dose level (0.05, 0.10, 0.2, 0.40, 0.80, 1.2, 1.6 and 2.0 mg/kg). All cohorts will receive injections of SBP-101 once daily Monday through Friday, for 3 weeks, followed by a 5-week rest period (3 weeks on and 5 weeks off = 1 cycle) for up to 5 cycles depending on response. Participants in the second part of this study (Phase 1b) will be administered SBP-101 at the maximum tolerated dose identified in Phase 1a for up to 5 cycles. SBP-101 is a small molecule which is similar to a compound, spermine, found naturally in human cells and important in cell survival / growth. Laboratory and animal studies suggest that SBP-101inhibits cell growth by substituting for spermine, suggesting that SBP-101 is a promising candidate for further development as a treatment for pancreatic cancer. Participants will be regularly assessed during treatment in order to assess safety and tolerability. Other goals of this study are to measure the levels of SBP-101 in the blood and urine over time and test whether SBP-101 can slow the growth of, or shrink tumours.
Interventions
SBP-101
During Phase 1a of the study, participants will be enrolled in each of 8 cohorts sequentially:
1) Cohort 1: SBP-101, 0.05 mg/kg subcutaneously, for up to 5 cycles
2) Cohort 2: SBP-101, 0.10 mg/kg subcutaneously, for up to 5 cycles
3) Cohort 3: SBP-101, 0.20 mg/kg subcutaneously, for up to 5 cycles
4) Cohort 4: SBP-101, 0.40 mg/kg subcutaneously, for up to 5 cycles
5) Cohort 5: SBP-101, 0.80 mg/kg subcutaneously, for up to 5 cycles
6) Cohort 6: SBP-101, 1.20 mg/kg subcutaneously, for up t
SBP-101 During Phase 1a of the study, participants will be enrolled in each of 8 cohorts sequentially: 1) Cohort 1: SBP-101, 0.05 mg/kg subcutaneously, for up to 5 cycles 2) Cohort 2: SBP-101, 0.10 mg/kg subcutaneously, for up to 5 cycles 3) Cohort 3: SBP-101, 0.20 mg/kg subcutaneously, for up to 5 cycles 4) Cohort 4: SBP-101, 0.40 mg/kg subcutaneously, for up to 5 cycles 5) Cohort 5: SBP-101, 0.80 mg/kg subcutaneously, for up to 5 cycles 6) Cohort 6: SBP-101, 1.20 mg/kg subcutaneously, for up to 3 cycles 7) Cohort 7: SBP-101, 1.60 mg/kg subcutaneously, for up to 2.5 cycles 8) Cohort 8: SBP-101, 2.00 mg/kg subcutaneously, for up to 2 cycles. All cohorts will receive subcutaneous injections of SBP-101 once daily Monday through Friday, for 3 weeks, followed by a 5- week rest period (3 weeks on, 5 weeks off = 1 cycle). Tumour assessment will be performed at the end of each cycle 1 and every 8 weeks thereafter. If the disease is stable or a partial response is seen, participants will continue to receive cycles of SBP-101 up to the maximum number of cycles specified above until disease progression or unacceptable toxicity, whichever comes first. If a participant has a complete response prior to receiving the maximum number of allowed cycles, one additional cycle will be administered. In Phase 1b of the study, an additional 24 participants will be enrolled at the maximum tolerated dose identified in Phase 1a to further establish the safety and tolerability of SBP-101 and to explore efficacy endpoints. Subjects in the phase 1b expansion study will receive SBP-101 subcutaneously on Monday through Friday for 3 weeks (15 doses per cycle) at the maximum tolerated dose (MTD) confirmed in Part 1a of this trial, repeated every 8 weeks (3 weeks on, 5 weeks off) for up to 5 cycles or a maximum cumulative dose of 60 mg/kg of treatment (depending on the MTD), or until disease progression or unacceptable toxicity, whichever comes first. If a participant has a complete response prior to receiving the maximum number of allowed cycles, one additional cycle will be administered.
Sponsors
Sun BioPharma Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed locally advanced or metastatic pancreatic ductal adenocarcinoma. Patients with acinar cell carcinoma may also be included. 2. Measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan by RECIST criteria (Phase 1b only) 3. ECOG Performance Status 0 or 1. 4. Received, and failed or were intolerant to at least 1 prior systemic therapy for locally advanced or metastatic pancreatic ductal adenocarcinoma 5. Adult, aged 18 years or older, male or female 6. 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 7. Adequate bone marrow, hepatic, renal and coagulation function 8. QTc interval less than or equal to 470 msec at Baseline 9. Willing and able to provide written informed consent.
Exclusion criteria
1. 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. 2. 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 3. Presence of islet-cell or pancreatic neuroendocrine tumor or mixed adenocarcinoma-neuroendocrine carcinoma 4. Symptomatic central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic subjects without history of CNS metastases is not required. 5. Serum albumin less than 30 g/L (3.0 g/dL) 6. Glycosylated hemoglobin (Hgb A1C) greater than 8.0% 7. Life expectancy less than 16 weeks 8. Presence of known active bacterial, fungal, or viral infection requiring systemic therapy 9. Known infection with human immunodeficiency virus (HIV), hepatitis B or C 10. Presence of interstitial lung disease, pulmonary fibrosis, or pulmonary hypersensitivity reaction 11. Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV 12. Maldigestion/malabsorption syndrome pre-dating the diagnosis of pancreatic cancer 13. Known existing coagulopathy or receiving anticoagulants 14. Pregnant or lactating 15. Major surgery within 4 weeks of the start of study treatment, without complete recovery 16. Participation in any other clinical investigation within 4 weeks of receiving the first dose of study drug.
Outcome results
None listed