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Dose-finding Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SNB-101(SN-38) in Patients With Tumors

Primary Purpose

Colorectal Cancer, Breast Cancer, Pancreas Cancer

Status

Recruiting

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

SNB-101

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring solid tumors

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

CHA Medical CenterRecruiting
The Severance Hospital of the Yonsei UniversityRecruiting
The Catholic University of Korea Seoul ST. Mary's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Cohort 6

Cohort 7

Arm Description

SNB-101 5/8mg/m2 Q2W IV

SNB-101 10/16mg/m2 Q2W IV

SNB-101 20/32mg/m2 Q2W IV

SNB-101 30/48mg/m2 Q2W IV

SNB-101 40/64mg/m2 Q2W IV

SNB-101 45/72mg/m2 Q2W IV

SNB-101 50/80mg/m2 Q2W IV

Outcomes

Primary Outcome Measures

Dose-limiting toxicity(DLT)

All participants who take at least 1 dose of SNB-101 will be assessed. DLTs will be presented by dose group and the MTD determined. *DLTs : 1) Hematological toxicity Grade 4 thrombocytopenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 neutropenia lasting > 7 days ≥ grade 3 febrile neutropenia 2) Nonhematological toxicity Any ≥ grade 3 nonhematological toxicity 3) Liver function abnormalities Patients who have bone or liver metastasis with the following increases will be considered a DLT: Baseline AST or ALT = 2.5 to 5× ULN, then AST or ALT that increases to >8× ULN Baseline ALP = 2.5 to 5×ULN, then ALP increases to >8×ULN 4) Any toxicity related to SNB-101 that results in a treatment delay of more than 2 weeks.

Permanent discontinuation of SNB-101 and dose reduction due to adverse events(AEs)

Definition of permanent discontinuation of SNB-101: Experiencing a DLT or intolerable toxicity during the DLT observation period. Experiencing life-threatening Grade 4 adverse events (AE). Experiencing Grade 2 interstitial lung disease or Grade 4 infusion related reaction/ hypersensitivity. Descriptive statistics for continuous variables, frequency and percentage for categorical variables

Number of participants with clinically meaningful changes in Laboratory test results from baseline

Hematology: RBC count, WBC count, hemoglobin, hematocrit, platelets, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, WBC differential count, ANC. Serum biochemistry: BUN, creatinine, glucose (random), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, total protein, albumin, Ca, P, K, Na, Cl, CO2, GGT, and LDH. Coagulation: prothrombin time and international normalized ratio. Viral serology: viral serology test for HIV antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus antibody. The test can be waived for participants who have results within 28 days prior to screening. Urinalysis: specific gravity, protein, pH, blood, and ketones. Descriptive statistics for continuous variables, frequency and percentage for categorical variables

Number of participants with clinically meaningful changes in Vital signs from baseline

Vital signs include blood pressure(sitSBP/sitDBP), heart rate, respiratory rate, and body temperature. Change from baseline or previous visit will be described. After each infusion of SNB-101, vital signs will be monitored every 30 minutes for 3 hours on an outpatient basis. Descriptive statistics for continuous variables, frequency and percentage for categorical variables

Electrocardiogram(ECG) results

ECG data will be collected at screening, C1D1, C3D1 and EOT. ECG measurement at C1D1 and C3D1 will be performed after PK sampling at the end of the infusion (90 min.), 2.5 hours and 24 hours after drug administration. ECG QT interval will be assessed for the safety endpoint(e.g. QTc prolongation) Descriptive statistics for continuous variables, frequency and percentage for categorical variables

Number of clinically significant Chest radiograph findings(chest x-ray, CXR)

Number of clinically significant chest radiograph findings from chest x-ray. Descriptive statistics for continuous variables, frequency and percentage for categorical variables

Secondary Outcome Measures

Area under the plasma concentration-time curve(AUC)

- The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Maximum plasma concentration(Cmax)

- The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Time to Cmax(Tmax)

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Clearance(CL)

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Volume of distribution(Vd)

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Terminal half-life(t1/2)

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Elimination rate constant

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

The objective response rate(ORR)

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. ORR is defined as the percentage of participants who have achieved either complete response or partial response to the therapeutic intervention. Response is measured per RECIST version 1.1 as assessed by the investigator at the local site. ORR will be presented as frequencies and percentages.

Disease control rate(DCR)

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. DCR is defined as the percentage of participants who have achieved either complete response, partial response, or stable disease to the therapeutic intervention. Response is measured per RECIST version 1.1 as assessed by the investigator at the local site. DCR will be presented as frequencies and percentages.

Overall survival(OS)

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. OS is defined as the time from the first dose of SNB-101 to death from any cause. OS median survival times will be calculated using the Kaplan Meier method.

Progression-free survival(PFS)

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. PFS is defined as the time from the first dose of SNB-101 to documented disease progression or death due to any cause, whichever occurs earlier. PFS median survival times will be calculated using the Kaplan Meier method.

Time to progression(TTP)

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. TTP is defined as the time from the first dose of SNB-101 to objective tumor progression. TTP will be calculated using the Kaplan Meier method.

Full Information

NCT ID

NCT04640480

First Posted

October 22, 2020

Last Updated

April 18, 2023

Sponsor

SN BioScience

1. Study Identification

Unique Protocol Identification Number

NCT04640480

Brief Title

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

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 21, 2020 (Actual)

Primary Completion Date

May 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

SN BioScience

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer, Breast Cancer, Pancreas Cancer, Ovarian Cancer, Small-cell Lung Cancer, Gastric Cancer, Head and Neck Cancer

Keywords

solid tumors

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

1-7 cohorts, dose escalation method according to modified accelerated titration design

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

SNB-101 5/8mg/m2 Q2W IV

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

SNB-101 10/16mg/m2 Q2W IV

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

SNB-101 20/32mg/m2 Q2W IV

Arm Title

Cohort 4

Arm Type

Experimental

Arm Description

SNB-101 30/48mg/m2 Q2W IV

Arm Title

Cohort 5

Arm Type

Experimental

Arm Description

SNB-101 40/64mg/m2 Q2W IV

Arm Title

Cohort 6

Arm Type

Experimental

Arm Description

SNB-101 45/72mg/m2 Q2W IV

Arm Title

Cohort 7

Arm Type

Experimental

Arm Description

SNB-101 50/80mg/m2 Q2W IV

Intervention Type

Drug

Intervention Name(s)

SNB-101

Other Intervention Name(s)

SN-38

Intervention Description

SN-38 dosage ranges from 1 to 7 will be determined by Safety Review Committee meeting

Primary Outcome Measure Information:

Title

Dose-limiting toxicity(DLT)

Description

Time Frame

up to 18 months(depending on safety variable)

Title

Permanent discontinuation of SNB-101 and dose reduction due to adverse events(AEs)

Description

Time Frame

up to 18 months(depending on safety variable)

Title

Number of participants with clinically meaningful changes in Laboratory test results from baseline

Description

Time Frame

up to 18 months(depending on safety variable)

Title

Number of participants with clinically meaningful changes in Vital signs from baseline

Description

Time Frame

up to 18 months(depending on safety variable)

Title

Electrocardiogram(ECG) results

Description

Time Frame

up to 18 months(depending on safety variable)

Title

Number of clinically significant Chest radiograph findings(chest x-ray, CXR)

Description

Number of clinically significant chest radiograph findings from chest x-ray. Descriptive statistics for continuous variables, frequency and percentage for categorical variables

Time Frame

up to 18 months(depending on safety variable)

Secondary Outcome Measure Information:

Title

Area under the plasma concentration-time curve(AUC)

Description

- The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Time Frame

4 months

Title

Maximum plasma concentration(Cmax)

Description

- The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Time Frame

4 months

Title

Time to Cmax(Tmax)

Description

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Time Frame

4 months

Title

Clearance(CL)

Description

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Time Frame

4 months

Title

Volume of distribution(Vd)

Description

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Time Frame

4 months

Title

Terminal half-life(t1/2)

Description

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Time Frame

4 months

Title

Elimination rate constant

Description

The PK parameter will be calculated for SN-38 based on plasma concentrations measured from the PK blood samples.

Time Frame

4 months

Title

The objective response rate(ORR)

Description

Time Frame

up to 18 months(depending on subject cycles)

Title

Disease control rate(DCR)

Description

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. DCR is defined as the percentage of participants who have achieved either complete response, partial response, or stable disease to the therapeutic intervention. Response is measured per RECIST version 1.1 as assessed by the investigator at the local site. DCR will be presented as frequencies and percentages.

Time Frame

up to 18 months(depending on subject cycles)

Title

Overall survival(OS)

Description

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. OS is defined as the time from the first dose of SNB-101 to death from any cause. OS median survival times will be calculated using the Kaplan Meier method.

Time Frame

up to 18 months(depending on subject cycles)

Title

Progression-free survival(PFS)

Description

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. PFS is defined as the time from the first dose of SNB-101 to documented disease progression or death due to any cause, whichever occurs earlier. PFS median survival times will be calculated using the Kaplan Meier method.

Time Frame

up to 18 months(depending on subject cycles)

Title

Time to progression(TTP)

Description

Determination of the antitumor efficacy of SNB-101 All participants who take at least 1 dose of SNB-101 and have at least 1 post dose efficacy assessment will be assessed. Computed tomography scans (abdomen/pelvic, chest) will be performed at screening and every 8 weeks (± 7 days) for tumor assessment. TTP is defined as the time from the first dose of SNB-101 to objective tumor progression. TTP will be calculated using the Kaplan Meier method.

Time Frame

up to 18 months(depending on subject cycles)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jaehong Kim

Phone

+82-31-757-3849

jhkim@snbioscience.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joohang Kim, Dr

Organizational Affiliation

CHA Medical Center at Bundang

Official's Role

Study Chair

Facility Information:

Facility Name

CHA Medical Center

City

Seongnam-si

State/Province

Gyeonggi-do

ZIP/Postal Code

13496

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joohang Kim, Dr

Facility Name

The Severance Hospital of the Yonsei University

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sunyoung Rha, Dr

Facility Name

The Catholic University of Korea Seoul ST. Mary's Hospital

City

Seoul

ZIP/Postal Code

06591

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Myung-ah Lee, Dr

12. IPD Sharing Statement

Learn more about this trial

Dose-finding Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SNB-101(SN-38) in Patients With Tumors

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