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A Phase 1 Study of ZSP1241 in Participants With Advanced Solid Tumors

Primary Purpose

Hepatocellular Carcinoma, Cholangiocarcinoma, Gastric Cancer

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ZSP1241
Sponsored by
Guangdong Zhongsheng Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants are required to meet all the criteria below in order to be included in the trial:

    1. Male or female patient, aged 18 ~ 75 years.
    2. Confirmed diagnosis of advanced solid tumors by histological or cytological examination, participants have no effective standard anticancer therapy available or is intolerant to standard anticancer therapy.
    3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
    4. Participants with at least 1 measurable tumor lesion based on RECIST 1.1.
    5. Recovery from past medical history of adverse reactions (excluding alopecia and neurotoxicity) caused by radiotherapy and/or chemotherapy to NCI CTCAE 5.0 Grade ≤ 1 or baseline level.
    6. Life expectancy ≥ 12 weeks.
    7. Adequate organ function, defined by the following laboratory results, to be obtained prior to enrollment:

      Bone marrow function: ANC≥1.5×109/L; HB≥90 g/L; PLT≥75×109/L. Liver function: ALT≤2.5×ULN, AST≤2.5×ULN, ALP≤2.5×ULN, TBIL≤1.5×ULN; ALT≤5×ULN, AST≤5×ULN (For participants with liver focal masses and metastasis).

      Renal function: creatinine≤1.5×ULN; CL≥ 50 mL/min. Coagulation function: INR≤1.5×ULN; INR≤2.3×ULN (For participants with liver focal masses and metastasis).

    8. Child-Pugh class A (only for hepatocellular carcinoma and cholangiocarcinoma).
    9. Participants (including partners) who have no gestation plans and are willing to follow reliable contraceptive measures during the study and until 8 months after the last dosing.
    10. Participants with voluntarily signature Informed Consent Form (ICF) prior to screening.

Exclusion Criteria:

  • Eligible participants must not meet any of the following exclusion criteria:

    1. Participants who have intracranial tumor and/or brain metastases with clinical symptoms needed treatment are ineligible not including the following :

      1. recovery from the therapy (including radiotherapy and/or surgery) 4 weeks before enrollment.
      2. participants with intracranial tumor who are clinically stable during screening and enrollment, no need to medication by hormone or anticonvulsants, and predicted to be clinically stable during the study.
    2. Participants who suffer from chronic and active infective diseases and require systemic antibiotic, antifungal, or antiviral treatment except concomitant antiviral systemic therapy for chronic hepatitis B or C.
    3. Participants with dysphagia.
    4. Participants with incontrollable hydrops in third lumen such as malignant pleural effusion and ascites.
    5. Participants with history of pulmonary fibrosis or interstitial pneumonia including pneumoconiosis and radiation pulmonary fibrosis beyond radiation field.
    6. Participants who suffer from irritable bowel syndrome and need medication.
    7. Participants with any clinically significant gastrointestinal abnormalities such as Crohn's disease, ulcerative colitis and subtotal gastrectomy.
    8. Participants with major surgery in recent 4 weeks or active peptic ulcer disease or unrecovered wound.
    9. Participants with history of myocardial infarction or congestive heart-failure (CHF) at NYHA≥3 level within 6 months prior to enrollment.
    10. Participants with LVEF<50% during screening.
    11. Participants with QTcF prolongations in ECG baseline ( QTcF>450ms for males or QTcF>470ms for females) or high risk factors leading to QT intervals prolonging (including hypokalemia, familial QT interval prolongation syndrome) or a history of uncontrollable blood pressure or a history of severe or uncontrollable ventricular arrhythmia such as two or three degree atrioventricular block.
    12. Participants with medications known as QTc prolongation or TDP ventricular tachycardia inducer or strong inhibitors and inducers of CYP3A4 not less than 5 days or 5 half-times before first dosing ZSP1241.
    13. Participants with history of most recently chemotherapy, radiotherapy, or non-antibody antitumor biologics within 4 weeks prior to the first ZSP1241 treatment and last time medication of nitrosoureas, mitomycin C or doxorubicin within 6 weeks and latest usage of antibody antitumor biologics within 4 weeks.
    14. Participants with current or prior retinal detachment or presently confirmed diagnosis keratopathy including but not limited to bullous keratopathy, calcific band keratopathy, corneal abrasion, keratohelcosis, keratitis and so on.
    15. Participants with history of autoimmune disease.
    16. Pregnant or nursing women.
    17. Participants who, in the judgment of the investigator, will be unfit for the study. ( For reasons such as poor compliance, unsuitable for venous catheterization and so on)

Sites / Locations

  • Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Part 1

Part 2 Cohort A

Part 2 Cohort B

Arm Description

Participants with advanced solid tumors including hepatocellular carcinoma, cholangiocarcinoma, gastric cancer, esophageal cancer, colorectal cancer and other advanced solid tumors.

Participants with hepatocellular carcinoma.

Participants with gastric cancer, esophageal cancer, colorectal cancer and other advanced solid tumor.

Outcomes

Primary Outcome Measures

Safety and tolerability of ZSP1241 in single dose ascending (SAD) and multiple dose ascending (MAD) as measured by assessment of maximum tolerated dose (MTD), dose limiting toxicity (DLT) and treatment emergent adverse events (TEAEs)
Participant with TEAEs assessed by CTCAE V5.0

Secondary Outcome Measures

Time to progression (TTP).
Overall response rate (ORR).
Cmax of ZSP1241
Defined as maximum observed plasma concentration
Tmax of ZSP1241
Defined as time to maximum plasma concentration
Cmin of ZSP1241
Defined as minimum observed plasma concentration during the dosing interval
AUC0-t of ZSP1241
Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration
t½ of ZSP1241
Defined as the apparent plasma terminal phase disposition half-life
Cl/F of ZSP1241
Defined as oral dose clearance

Full Information

First Posted
November 5, 2018
Last Updated
July 20, 2020
Sponsor
Guangdong Zhongsheng Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03734926
Brief Title
A Phase 1 Study of ZSP1241 in Participants With Advanced Solid Tumors
Official Title
A Phase 1, Open-Label, Dose-Escalation and Expansion, Safety and Tolerability Study of ZSP1241 in Participants With Advanced Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 13, 2018 (Actual)
Primary Completion Date
October 31, 2021 (Anticipated)
Study Completion Date
October 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guangdong Zhongsheng Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics, and determine the maximum tolerated dose of ZSP1241 in participants with hepatocellular carcinoma, cholangiocarcinoma, gastric cancer, esophageal cancer, colorectal cancer and other advanced solid tumors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Cholangiocarcinoma, Gastric Cancer, Esophageal Cancer, Colorectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1
Arm Type
Experimental
Arm Description
Participants with advanced solid tumors including hepatocellular carcinoma, cholangiocarcinoma, gastric cancer, esophageal cancer, colorectal cancer and other advanced solid tumors.
Arm Title
Part 2 Cohort A
Arm Type
Experimental
Arm Description
Participants with hepatocellular carcinoma.
Arm Title
Part 2 Cohort B
Arm Type
Experimental
Arm Description
Participants with gastric cancer, esophageal cancer, colorectal cancer and other advanced solid tumor.
Intervention Type
Drug
Intervention Name(s)
ZSP1241
Intervention Description
ZSP1241 tablets for oral administration.
Primary Outcome Measure Information:
Title
Safety and tolerability of ZSP1241 in single dose ascending (SAD) and multiple dose ascending (MAD) as measured by assessment of maximum tolerated dose (MTD), dose limiting toxicity (DLT) and treatment emergent adverse events (TEAEs)
Description
Participant with TEAEs assessed by CTCAE V5.0
Time Frame
At Day 7 for SAD Part and At day 28 after for MAD part
Secondary Outcome Measure Information:
Title
Time to progression (TTP).
Time Frame
Screening, Day 28 of Cycle 1 (28 days), then every 6 weeks for hepatocellular carcinoma or 8 weeks for other advanced solid tumors, until disease progression or discontinuation from study (up to 18 months).
Title
Overall response rate (ORR).
Time Frame
Screening, Day 28 of Cycle 1 (28 days), then every 6 weeks for hepatocellular carcinoma or 8 weeks for other advanced solid tumors, until disease progression or discontinuation from study (up to 18 months).
Title
Cmax of ZSP1241
Description
Defined as maximum observed plasma concentration
Time Frame
Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject.
Title
Tmax of ZSP1241
Description
Defined as time to maximum plasma concentration
Time Frame
Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject.
Title
Cmin of ZSP1241
Description
Defined as minimum observed plasma concentration during the dosing interval
Time Frame
Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject.
Title
AUC0-t of ZSP1241
Description
Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration
Time Frame
Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject.
Title
t½ of ZSP1241
Description
Defined as the apparent plasma terminal phase disposition half-life
Time Frame
Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject.
Title
Cl/F of ZSP1241
Description
Defined as oral dose clearance
Time Frame
Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants are required to meet all the criteria below in order to be included in the trial: Male or female patient, aged 18 ~ 75 years. Confirmed diagnosis of advanced solid tumors by histological or cytological examination, participants have no effective standard anticancer therapy available or is intolerant to standard anticancer therapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Participants with at least 1 measurable tumor lesion based on RECIST 1.1. Recovery from past medical history of adverse reactions (excluding alopecia and neurotoxicity) caused by radiotherapy and/or chemotherapy to NCI CTCAE 5.0 Grade ≤ 1 or baseline level. Life expectancy ≥ 12 weeks. Adequate organ function, defined by the following laboratory results, to be obtained prior to enrollment: Bone marrow function: ANC≥1.5×109/L; HB≥90 g/L; PLT≥75×109/L. Liver function: ALT≤2.5×ULN, AST≤2.5×ULN, ALP≤2.5×ULN, TBIL≤1.5×ULN; ALT≤5×ULN, AST≤5×ULN (For participants with liver focal masses and metastasis). Renal function: creatinine≤1.5×ULN; CL≥ 50 mL/min. Coagulation function: INR≤1.5×ULN; INR≤2.3×ULN (For participants with liver focal masses and metastasis). Child-Pugh class A (only for hepatocellular carcinoma and cholangiocarcinoma). Participants (including partners) who have no gestation plans and are willing to follow reliable contraceptive measures during the study and until 8 months after the last dosing. Participants with voluntarily signature Informed Consent Form (ICF) prior to screening. Exclusion Criteria: Eligible participants must not meet any of the following exclusion criteria: Participants who have intracranial tumor and/or brain metastases with clinical symptoms needed treatment are ineligible not including the following : recovery from the therapy (including radiotherapy and/or surgery) 4 weeks before enrollment. participants with intracranial tumor who are clinically stable during screening and enrollment, no need to medication by hormone or anticonvulsants, and predicted to be clinically stable during the study. Participants who suffer from chronic and active infective diseases and require systemic antibiotic, antifungal, or antiviral treatment except concomitant antiviral systemic therapy for chronic hepatitis B or C. Participants with dysphagia. Participants with incontrollable hydrops in third lumen such as malignant pleural effusion and ascites. Participants with history of pulmonary fibrosis or interstitial pneumonia including pneumoconiosis and radiation pulmonary fibrosis beyond radiation field. Participants who suffer from irritable bowel syndrome and need medication. Participants with any clinically significant gastrointestinal abnormalities such as Crohn's disease, ulcerative colitis and subtotal gastrectomy. Participants with major surgery in recent 4 weeks or active peptic ulcer disease or unrecovered wound. Participants with history of myocardial infarction or congestive heart-failure (CHF) at NYHA≥3 level within 6 months prior to enrollment. Participants with LVEF<50% during screening. Participants with QTcF prolongations in ECG baseline ( QTcF>450ms for males or QTcF>470ms for females) or high risk factors leading to QT intervals prolonging (including hypokalemia, familial QT interval prolongation syndrome) or a history of uncontrollable blood pressure or a history of severe or uncontrollable ventricular arrhythmia such as two or three degree atrioventricular block. Participants with medications known as QTc prolongation or TDP ventricular tachycardia inducer or strong inhibitors and inducers of CYP3A4 not less than 5 days or 5 half-times before first dosing ZSP1241. Participants with history of most recently chemotherapy, radiotherapy, or non-antibody antitumor biologics within 4 weeks prior to the first ZSP1241 treatment and last time medication of nitrosoureas, mitomycin C or doxorubicin within 6 weeks and latest usage of antibody antitumor biologics within 4 weeks. Participants with current or prior retinal detachment or presently confirmed diagnosis keratopathy including but not limited to bullous keratopathy, calcific band keratopathy, corneal abrasion, keratohelcosis, keratitis and so on. Participants with history of autoimmune disease. Pregnant or nursing women. Participants who, in the judgment of the investigator, will be unfit for the study. ( For reasons such as poor compliance, unsuitable for venous catheterization and so on)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ruihua Xu, MD
Phone
+862087343333
Email
xurh@sysucc.org.cn
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruihua XU, MD
Phone
+862087343333
Email
xurh@sysucc.org.cn

12. IPD Sharing Statement

Learn more about this trial

A Phase 1 Study of ZSP1241 in Participants With Advanced Solid Tumors

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