Clinical trial NCT04640480: Dose-finding Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SNB-101(SN-38) in Patients With Tumors
Official title: A Phase I, Open-Label, Dose-finding Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenously Infused SNB-101(as SN-38) in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer
Breast Cancer
Pancreas Cancer
Ovarian Cancer
Small-cell Lung Cancer
Gastric Cancer
Head and Neck Cancer
Keywords: solid tumors
Lead sponsor: SN BioScience
Sponsor class: INDUSTRY
First posted: 2020-11-23
Enrollment: 36
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 1-7 cohorts, dose escalation method according to modified accelerated titration design
Primary purpose: TREATMENT

Brief summary: SNB-101 is a novel nano-particle formulation of SN-38, the active metabolite of irinotecan(CPT-11). Study SNB101P01 is a multicenter, open-label, dose escalation, phase 1 study of SNB 101 with its active ingredient SN-38, in participants with advanced solid tumors. Dose escalation will occur using a modified accelerated titration design (ATD).

All participants will receive SNB 101 in different cohorts. SNB 101 will be administered intravenously to participants on day 1 and day 15 of each 28 day treatment cycle until progressive disease, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.

A Safety Review Committee will determine dose escalation, de-escalation, and modification and the MTD/RP2D based on DLTs and other safety information.

Detailed description: Each participant will undergo a screening period, a treatment period, and a follow-up period. Participants will be followed until death, withdrawal of consent, or end of study, whichever occurs first.

During the treatment period, participants will receive SNB-101 (dose range: 5 mg/m2 to 50 mg/m2) intravenously on day 1 and day 15 of each 28 day cycle.

Dose reductions are permitted after the DLT observation period, which occurs during the first 28 days of treatment (cycle 1). Participants may permanently or temporarily (at the investigator's discretion) discontinue SNB-101. If a participant experiences a DLT or unacceptable toxicity, SNB-101 treatment should be interrupted until the observed toxicity returns to baseline or ≤ grade 1 toxicity. The start of the next cycle can be delayed up to 2 weeks at the investigator's discretion.

Eligibility criteria: Inclusion Criteria:

* Patients with a histologically or cytologically confirmed, locally advanced or metastatic disease, has progressed after systemic standard of care treatment for advanced disease and is not suitable for complete surgical resection.
* Patients with measurable or evaluable disease consistent with Response Evaluation Criteria in Solid Tumors version 1.1.
* Patients ambulatory with an Eastern Cooperative Oncology Group performance score of 0 or 1.
* Patients with adequate hematological, renal, and liver function(CTCAE V5.0 grade 1 or lower).
* Patients with the life expectancy of 3 months or longer.

Exclusion Criteria:

* Patients homozygous for UGT1A1\*28 or UGT1A1\*6 alleles.
* Patients known or suspected intolerance or hypersensitivity to main ingredient or any of the excipients of SNB-101.
* Patients with unintentional weight loss \>10% within 3 months prior to screening.
* Patients who are on dialysis.
* Patients who are positive for HIVs.
* Patients with a QT interval with Fridericia's correction outside of normal.
* Patients with intestinal palsy or bowel obstruction.
* Patients with chronic inflammatory bowel disease.
* Patients who may require administration of neuromuscular blockers, peripheral muscle relaxants, etc. during the study.
* Patients who may require lapatinib during the study.
* Patients who may require attenuated vaccine during the study.
* Patients who are taking any medication that in the judgement of the investigator could have an effect on the action of SNB-101.
* Patients unable to participate in the study as judged by the investigator.

Primary outcomes:
measure: Dose-limiting toxicity(DLT)
timeFrame: up to 18 months(depending on safety variable)
measure: Permanent discontinuation of SNB-101 and dose reduction due to adverse events(AEs)
timeFrame: up to 18 months(depending on safety variable)
measure: Number of participants with clinically meaningful changes in Laboratory test results from baseline
timeFrame: up to 18 months(depending on safety variable)
measure: Number of participants with clinically meaningful changes in Vital signs from baseline
timeFrame: up to 18 months(depending on safety variable)
measure: Electrocardiogram(ECG) results
timeFrame: up to 18 months(depending on safety variable)
measure: Number of clinically significant Chest radiograph findings(chest x-ray, CXR)
timeFrame: up to 18 months(depending on safety variable)
Secondary outcomes:
measure: Area under the plasma concentration-time curve(AUC)
timeFrame: 4 months
measure: Maximum plasma concentration(Cmax)
timeFrame: 4 months
measure: Time to Cmax(Tmax)
timeFrame: 4 months
measure: Clearance(CL)
timeFrame: 4 months
measure: Volume of distribution(Vd)
timeFrame: 4 months
measure: Terminal half-life(t1/2)
timeFrame: 4 months
measure: Elimination rate constant
timeFrame: 4 months
measure: The objective response rate(ORR)
timeFrame: up to 18 months(depending on subject cycles)
measure: Disease control rate(DCR)
timeFrame: up to 18 months(depending on subject cycles)
measure: Overall survival(OS)
timeFrame: up to 18 months(depending on subject cycles)
measure: Progression-free survival(PFS)
timeFrame: up to 18 months(depending on subject cycles)
measure: Time to progression(TTP)
timeFrame: up to 18 months(depending on subject cycles)
Other outcomes:
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: CHA Medical Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: The Severance Hospital of the Yonsei University
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul ST. Mary's Hospital
Study officials:
affiliation: CHA Medical Center at Bundang
name: Joohang Kim, Dr
role: STUDY_CHAIR
References: