ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03734926
Recruitment Status : Not yet recruiting
First Posted : November 8, 2018
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
Guangdong Zhongsheng Pharmaceutical Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Cholangiocarcinoma Gastric Cancer Esophageal Cancer Colorectal Cancer Drug: ZSP1241 Phase 1

Study Type : Interventional
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose-Escalation and Expansion, Safety and Tolerability Study of ZSP1241 in Participants With Advanced Solid Tumors
Estimated Study Start Date : November 20, 2018
Estimated Primary Completion Date : October 20, 2020
Estimated Study Completion Date : November 20, 2020


Arm Intervention/treatment
Experimental: Part 1
Participants with advanced solid tumors including hepatocellular carcinoma, cholangiocarcinoma, gastric cancer, esophageal cancer, colorectal cancer and other advanced solid tumors.
Drug: ZSP1241
ZSP1241 tablets for oral administration.

Experimental: Part 2 Cohort A
Participants with hepatocellular carcinoma.
Drug: ZSP1241
ZSP1241 tablets for oral administration.

Experimental: Part 2 Cohort B
Participants with gastric cancer, esophageal cancer, colorectal cancer and other advanced solid tumor.
Drug: ZSP1241
ZSP1241 tablets for oral administration.




Primary Outcome Measures :
  1. 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) [ Time Frame: At Day 7 for SAD Part and At day 28 after for MAD part ]
    Participant with TEAEs assessed by CTCAE V5.0


Secondary Outcome Measures :
  1. 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). ]
  2. 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). ]
  3. Cmax of ZSP1241 [ Time Frame: Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject. ]
    Defined as maximum observed plasma concentration

  4. Tmax of ZSP1241 [ Time Frame: Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject. ]
    Defined as time to maximum plasma concentration

  5. Cmin of ZSP1241 [ Time Frame: Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject. ]
    Defined as minimum observed plasma concentration during the dosing interval

  6. AUC0-t of ZSP1241 [ Time Frame: Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject. ]
    Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration

  7. t½ of ZSP1241 [ Time Frame: Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject. ]
    Defined as the apparent plasma terminal phase disposition half-life

  8. Cl/F of ZSP1241 [ Time Frame: Protocol-defined time points during Cycles 0 (7 days) and 1 (28 days) of treatment per subject. ]
    Defined as oral dose clearance



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Participants with history of allergic reactions to ZSP1241, any of the excipients of ZSP1241 or similar compounds.
    17. Pregnant or nursing women.
    18. 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03734926


Contacts
Contact: Ruihua Xu, MD +862087343333 xurh@sysucc.org.cn

Locations
China, Guangdong
Sun Yat-sen University Cancer Center Not yet recruiting
Guangzhou, Guangdong, China, 510060
Contact: Ruihua XU, MD    +862087343333    xurh@sysucc.org.cn   
Sponsors and Collaborators
Guangdong Zhongsheng Pharmaceutical Co., Ltd.

Responsible Party: Guangdong Zhongsheng Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT03734926     History of Changes
Other Study ID Numbers: ZSP1241-18-01
First Posted: November 8, 2018    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Colorectal Neoplasms
Carcinoma, Hepatocellular
Stomach Neoplasms
Esophageal Neoplasms
Cholangiocarcinoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Liver Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases