A Phase 1, Open-Label, Dose-Escalation and Expansion, Safety and Tolerability Study of ZSP1602 in Participants With Advanced Solid Tumors

Guangdong Zhongsheng Pharmaceutical Co., Ltd.1 site in 1 country65 target enrollmentJanuary 25, 2019

ConditionsBasal Cell Carcinoma Medulloblastoma Adenocarcinoma of Esophagogastric Junction Small Cell Lung Cancer Neuroendocrine Neoplasm Glioblastoma

InterventionsZSP1602

DrugsZSP1602

Overview

Phase: Phase 1
Intervention: ZSP1602
Conditions: Basal Cell Carcinoma
Sponsor: Guangdong Zhongsheng Pharmaceutical Co., Ltd.
Enrollment: 65
Locations: 1
Primary Endpoint: Dose-limiting Toxicity (DLT)
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics, and determine the maximum tolerated dose of ZSP1602 in participants with basal cell carcinoma, adenocarcinoma of esophagogastric junction, small cell lung cancer, neuroendocrine neoplasm and other advanced solid tumors.

Registry

clinicaltrials.gov

Start Date

January 25, 2019

End Date

July 31, 2021

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Guangdong Zhongsheng Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants are required to meet all the criteria below in order to be included in the trial:
•Male or female participants, 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. For Part 1 Dose Ascending Stage, and Part 2 Dose expansion Stage:
•For Part 1: Advanced solid tumors including basal cell carcinoma and medulloblastoma, regardless of SMO or Gli1 alteration status.
•For Part 2: Participants will be enrolled into cohort A and cohort B. Cohort A: Participants with Adenocarcinoma of Esophagogastric Junction with SMO or Gli1 protein overexpression alteration. (IHC≥1%) Cohort B: Participants with basal cell carcinoma, small cell lung cancer, neuroendocrine neoplasm and glioblastoma with SMO or Gli1 protein overexpression alteration. (IHC≥1%)
•Eastern Cooperative Oncology Group (ECOG) performance status of 0-
•Participants with at least 1 measurable tumor lesion based on response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and response assessment in neuro-oncology criteria (RANO) (participants with glioblastoma must accept skull MRI scanning.)
•Recovery from past medical history of adverse reactions (excluding alopecia and neurotoxicity) caused by radiotherapy and chemotherapy to national cancer institute common terminology criteria for adverse events 4.03 (NCI CTCAE 4.03) ≤Grade 1 or baseline level.
•Life expectancy \> 12 weeks.
•Adequate organ function, defined by the following laboratory results, to be obtained prior to registration and enrollment:

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 and need treatment are ineligible except for the following circumstances:
•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, have no need to medication by hormone or anticonvulsants, and are estimated to be clinically stable during the study.
•Participants with glioblastoma confirmed diagnosis via MRI or CT of intracranial hemorrhage and intratumor hemorrhage.
•Participants with positive human immunodeficiency virus(HIV) or hepatitis C virus antibody (HCV) or hepatitis B surface antigen (HBV DNA\>2.0 ×103 IU/ml) or active infections which require systematic antibiotics therapy or concurred with unexplainable fever before drug treatment.
•History of pulmonary fibrosis or interstitial pneumonia including pneumoconiosis and radiation pulmonary fibrosis beyond radiation field.
•Participants with dysphagia.
•Participants with incontrollable hydrops in third lumen such as malignant pleural effusion and ascites.
•Participants with Diarrhea \> Grade 2 (according to CTCAE 4.03)

Arms & Interventions

Part 1

Participants with advanced solid tumors including basal cell carcinoma and medulloblastoma, regardless of SMO or Gli1 alteration status.

Intervention: ZSP1602

Part 2 Cohort A

Participants with Adenocarcinoma of Esophagogastric Junction with SMO or Gli1 protein overexpression alteration.

Intervention: ZSP1602

Part 2 Cohort B

Participants with basal cell carcinoma, small cell lung cancer, neuroendocrine neoplasm and glioblastoma with SMO or Gli1 protein overexpression alteration.

Intervention: ZSP1602

Outcomes

Primary Outcomes

Dose-limiting Toxicity (DLT)

Time Frame: At day 32 after first dosing.

To determine the DLT of ZSP1602 in advanced solid tumor participants accessed by CTCAE4.03

Maximum tolerated dose (MTD)

Time Frame: At day 32 after first dosing.

The highest dose at the level with \<= 2/6 participants experienced DLT.

Secondary Outcomes

Cmax of ZSP1602(Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants.)
Tmax of ZSP1602(Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants.)
Cmin of ZSP1602(Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants.)
AUC0-t of ZSP1602(Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants.)
T1/2 of ZSP1602(Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants.)
Time to progression (TTP)(From Screening, Day 28 of Cycle1 (28 days), then every 8 weeks, until disease progression or discontinuation from study (approximately 18 months or earlier if participants terminate from the study).)
Over all response (ORR)(From Screening, Day 28 of Cycle1 (28 days), then every 8 weeks, until disease progression or discontinuation from study (approximately 18 months or earlier if participants terminate from the study).)
Cl/F of ZSP1602(Protocol-defined time points during Cycles 0 (4 days) and 1 (28 days) of treatment per participants.)