An Open-label Phase I/II Clinical Trial of PT-112 Injection for Advanced Solid Tumors and Advanced Hepatocellular Carcinoma

NCT03439761 | Unknown Phase 1

• 1 other identifier: SCI-PT112-ONC-P1-002
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

Use PT-112 alone for Phase I dose escalation stage: advanced solid tumors, Phase I dose confirmation stage: advanced solid tumors. Phase II hepatocellular carcinoma (HCC). To evaluate the safety and tolerability of PT-112 injection from 250mg/m2 dose level with 3+3 dose escalation design, find Maximum tolerated dose (MTD), Recommended Phase II Dose(RP2D) and evaluate the Pharmacokinetic (PK) profile of PT-112 through Phase I dose escalation stage. Phase I dose confirmation stage: evaluate the safety and tolerability of PT-112 with RP2D, evaluate the anti-tumor effect of PT-112 at RP2D. Phase II stage: evaluate the anti-tumor effect of PT-112 at RP2D in advanced HCC

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Adverse Event (AE)

  The primary outcome for Phase I dose escalation stage

  Informed consent form (ICF) signed till 28days after end of treatment

• Dose Limited Toxicity (DLT)

  The primary outcome for Phase I dose escalation stage

  First dose till 28days after 1st dosing. (1st cycle treatment)

• AE

  The primary outcome for Phase I dose confirmation stage

  ICF signed till 28days after end of treatment

• Disease Control Rate (DCR)

  The primary outcome for Phase II (rate of complete response(CR)+partial response (PR)+stable disease(SD))

  subject enrolled till disease progress estimate 6 months after first dosing.

Secondary Outcomes (7)

• DCR

  subject enrolled till disease progress estimate 6 months after first dosing.

• Objective Response Rate (ORR)

  subject enrolled till disease progress estimate 6 months after first dosing.

• Progress Free Survival(PFS)

  enrolled study till first disease progress estimate 6 months after first dosing.

• Peak Plasma Concentration （Cmax）

  collect PK blood sample in first and second cycles (28 and 56 days after 1st dosing)

• Area under the plasma concentration versus time curve (AUC)

  collect PK blood sample in first and second cycles (28 and 56 days after 1st dosing)

Study Arms (1)

PT-112 Injection

EXPERIMENTAL

PT-112 Injection alone

Drug: PT-112 Injection

Interventions

PT-112 Injection DRUG

PT-112 Injection 28 days constitute a period. The drug is intravenously dripped for 60 minutes at the 1st, 8th and 15th day of each period.

PT-112 Injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old and ≤ 75 years old, male or female
• Local advanced or metastatic solid tumors confirmed by histopathology or cytology that do not respond to standard treatment or have no standard effective treatment (including but not limited to hepatocellular carcinoma, gastric cancer, colorectal cancer, non-small cell lung cancer, head and neck cancer, and breast cancer)
• Compliance with the requirements for type of tumor in the group in dose confirmation stage;
• Eastern Cooperative Oncology Group (ECOG) physical score: 0 or 1
• Lesions that can be assessed by imaging according to the Response evaluation criteria in solid tumors (RECIST) 1.1 (not required in dose escalation stage);
• Expected survival\>12 weeks;
• Generally normal bone marrow reserve: absolute neutrophil count (ANC)
• ≥1.5\*10\^9/L, platelet count≥100\*10\^9/L and hemoglobin≥90 g/L; Generally normal liver function: serum albumin ≥3.0 g/dL; bilirubin ≤1.5×upper limits of normal (ULN), Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5×ULN, ALT or AST ≤5×ULN for patients with liver metastases or primary liver cancer; Normal renal function: creatinine ≤1.5×ULN or creatinine clearance ≥60ml/min (according to Cockcroft-Gault formula); Generally normal coagulation function: International Normalized Ratio(INR)≤1.5×ULN, activated partial thromboplastin time (APTT) ≤1.5×ULN; Cardiac function: Left ventricular ejection fraction (LVEF)≥ 50%;
• Subjects with history of brain metastases who are diagnosed with stable disease not requiring treatment with steroid or anticonvulsant, regardless of previous radiotherapy;
• Signing of informed consent form before participation in the study.
• Advanced HCC diagnosed by histopathology or cytology that cannot be surgically removed or progresses after intervention/local treatment, previous treatment with one systemic anti-cancer chemotherapy, Barcelona Clinic Liver Cancer (BCLC) staging: Stage C, Child-Pugh A and mild grade B (≤7);
• Lesions that can be assessed by imaging according to the RECIST 1.1;

You may not qualify if:

• Untreated active hepatitis (hepatitis B: HBsAg positive with abnormal liver function and hepatitis B virus(HBV)-DNA ≥ 2000international unit (IU)/ml; hepatitis C: hepatitis C virus (HCV)-RNA positive and abnormal liver function);
• antitumor immunoregulation therapy, immunosuppressive therapy, corticosteroids \> 20 mg/day (unless used to prevent contrast agent reactions during radiotherapy), growth factor therapy (such as erythropoietin) or transfusion therapy within 14 days before use of the investigational drug;
• Unrecovered toxic and side effects caused by previous treatment (CTCAE ≤ grade 1), except hair loss and other tolerable events judged by the investigators;
• Any grade of peripheral neuropathy within 28 days prior to use of the investigational drug;
• Known allergy or hypersensitivity to platinum drugs;
• Antitumor therapy like chemotherapy, biotherapy, radiotherapy, endocrine therapy, target therapy (except Nitrourea, mitomycin C) within 4 weeks before use of the investigational drug. Use Nitrourea or mitomycin C within 6 weeks before use of the investigational drug.
• Major surgery within 28 days before use of the investigational drug;
• Acute bacterial, viral or fungal infections requiring systemic treatment or unexplained fever during screening before the first administration of drug (body temperature\> 38.5℃);
• Moderate or massive effusion of body cavity need treatment;
• History of mental illness;
• Human Immunodeficiency Virus(HIV) carriers or Acquired Immune Deficiency Syndrome (AIDS) patients;
• Any of the following conditions within six months before sign informed consent form : uncontrolled congestive heart failure (New York Heart Association grade 2 or 4), angina pectoris, myocardial infarction, stroke (except lacunar infarction), coronary/peripheral artery bypass surgery, pulmonary embolism);
• Uncontrolled arrhythmia or persistent QT interval prolongation, \> 450 ms for men or \> 470 ms for women;
• Use of any investigational drug or device within 28 days before the use of investigational drug;
• Pregnant or lactating women;

Sponsors & Collaborators

• SciClone Pharmaceuticals: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200123, China

RECRUITING

Study Officials

• Jin Li, MD

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Crystal Qin, MD, PhD

CONTACT

86-021-23193802; cqin@sciclone.com

Jin Li, MD

CONTACT

86-021-38804518; tianyoulijin@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: PT-112 injection alone-chemotherapy

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: February 20, 2018
• Study Start: March 7, 2018
• Primary Completion: May 1, 2020
• Study Completion: July 1, 2020
• Last Updated: March 16, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)