Brief Title
PT-112 (Phosplatin's Platinum) Combine With Gemcitabine Injection for Advanced Solid Tumors
Official Title
An Open-label Phase I/II Clinical Trial of PT-112 Combine With Gemcitabine Injection for Advanced Solid Tumors
Brief Summary
Phase I dose escalation period: solid tumors, including but not limited to biliary tract
cancer, pancreatic cancer, ovarian cancer, thymoma, neuroendocrine carcinoma and other
advanced solid tumors.
Phase II trial period: biliary tract cancer
Detailed Description
This is a multicenter, open-label, phase I/ II clinical study, including phase I dose
escalation period and phase II trial period.
The phase I dose escalation period will adopt a 3+3 dose escalation design. Three dose groups
are designed as follows:
Level 1: 150 mg/m2 PT-112 (Phosplatin's platinum) + 1000 mg/m2 gemcitabine; Level 2: 200
mg/m2 PT-112 + 1000 mg/m2 gemcitabine; Level 3: 250 mg/m2 PT-112 + 1000 mg/m2 gemcitabine. If
any DLT(Dose-Limiting Toxicity ) occurs in Level 1 group during dose escalation, the dose
will be down titrated to Level-1 150 mg/m2 PT-112 + 800 mg/m2 gemcitabine. After the lowest
dose group (Level-1 or Level 1), the dose of gemcitabine will be fixed while the dose of
PT-112 will be up titrated.
During the phase I dose escalation period, sufficient data will be obtained to demonstrate
that the dose is safe. Investigators and sponsor will discuss and decide the initiation time
of the phase II period. In phase II, it is planned to enroll subjects with biliary tract
cancer according to Simon's two-stage study design, to assess the safety and anti-tumor
efficacy of PT-112 in combination with gemcitabine for treating patients with advanced
biliary tract cancer. In the first period, 23 evaluable subjects are intended to be enrolled.
If ≤ 12 subjects have disease control (CR(Complete Response) + PR(Partial Response) +
SD(Stable Disease)) at the first post-baseline tumor assessment, the study drug will be
considered to be ineffective and the trial terminated; if >12 subjects have disease control
(CR + PR + SD), the enrollment for phase II will be initiated. In total, 37 evaluable
subjects will be enrolled. The study drug will be considered to be ineffective if a total of
≤23 subjects have disease control (CR + PR + SD).
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Define the recommended dose level for PT-112(Phase I)
Secondary Outcome
Anti-tumor efficacy evaluation (Phase I)
Condition
Biliary Tract Cancer
Intervention
PT-112
Study Arms / Comparison Groups
PT-112 in Combination with Gemcitabine Injection
Description: PT-112 in combination with Gemcitabine injection for the treatment of patients with advanced solid tumors
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
68
Start Date
April 13, 2020
Completion Date
April 28, 2023
Primary Completion Date
August 30, 2022
Eligibility Criteria
Inclusion Criteria:
1. Male or female aged 18-75 years (18 and 75 years included).
2. For phase I dose escalation period only: patients with locally advanced or metastatic
solid tumors (including but not limited to biliary tract cancer, pancreatic cancer,
ovarian cancer, etc.) confirmed by histopathology or cytology who have failed to
respond to standard regimen or have no standard regimen.
3. ECOG(Eastern Cooperative Oncology Group) performance status score of 0-1.
4. Expected survival time greater than 12 weeks.
5. Subjects must have proper organ function and laboratory test results meet the
following standards prior to enrollment:
- Basically normal bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 ×
109/ L, platelet ≥ 100 × 109/ L, and hemoglobin ≥ 90 g/ L;
- Basically normal liver function: serum albumin ≥ 3.0 g/dL; bilirubin ≤ 1.5 ×
ULN(upper limit of normal ), ALT(Alanine aminotransferase) and AST( Aspartate
transaminase) ≤ 2.5 × ULN; if the patients suffer from liver metastasis or
primary liver cancer, ALT or AST ≤ 5 × ULN;
- Normal renal function: creatinine ≤ 1.5 × ULN or creatinine clearance (CL) ≥ 60
mL/min (according to Cockcroft-Gault formula); .Basically normal coagulation
function: INR(international normalized ratio) ≤ 1.5 × ULN, APTT(activated partial
thromboplastin time) ≤ 1.5 × ULN.
6. Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%.
7. subjects with a history of brain metastases who are diagnosed as stable disease by the
investigator and do not require additional steroids or anticonvulsants, with
radiotherapy or without treatment.
8. Negative serum β-HCG(human chorionic gonadotropin) test for women of childbearing
potential (defined as women aged less than 50 years or over 50 years and amenorrheic
for less than 12 months prior to screening).
9. Subjects must give informed consent for the study prior to the test and sign the
informed consent form.
Additional inclusion criteria applicable to phase II trial period:
10. Patients with histologically or cytologically confirmed unresectable or metastatic
biliary tract cancer, including intrahepatic cholangiocarcinoma (IHCC), extrahepatic
cholangiocarcinoma (EHCC), and gallbladder carcinoma (GBC).
11. Patients who have not received systemic treatment for unresectable or metastatic
biliary tract cancer or received only one systemic anti-tumor chemotherapy regimen;
patients who have received one adjuvant or neoadjuvant chemotherapy regimen and
relapsed more than 6 months after the end of chemotherapy can be enrolled.
Exclusion Criteria:
1. Positive HIV antibody.
2. Active hepatitis, (hepatitis B: HBsAg positive with abnormal liver function and
HBV(hepatitis B virus )-DNA ≥ 1000 IU/ml; hepatitis C: HCV(hepatitis C virus)-RNA
positive with abnormal liver function).
3. Treatment with corticosteroids > 20 mg/ day prednisone or other equivalent hormone
(unless used to prevent contrast media reactions during radiological procedures),
growth factors (eg, erythropoietin, granulocyte colony-stimulating factor, recombinant
human thrombopoietin), blood transfusion.
4. The toxic and side effects caused by the subject's previous treatment not recovered to
CTCAE Grade ≤ 1, except for alopecia and other events judged to be tolerable by the
investigator.
5. Peripheral neuropathy of any grade within 28 days prior to the initiation of study
drug.
6. Patients with known sensitivity or hypersensitivity to platinum drugs and/ or
gemcitabine.
7. Having received a major surgery within 28 days prior to the initiation of study drug.
8. Having received chemotherapy, biotherapy, radiotherapy, endocrine therapy and targeted
anti-tumor therapy (except for nitrosoureas and mitomycin C) within 28 days prior to
the initiation of study drug; received nitrosoureas or mitomycin C within 6 weeks
prior to the initiation of study drug; received palliative local radiotherapy within 1
week prior to the initiation of study drug; received Chinese herbal medicine with
anti-tumor effect within 1 week before the initiation of the study drug.
9. Patients with uncontrollable hypertension (normal range for diastolic blood pressure
60-90 mmHg and for systolic blood pressure 90-140 mmHg ).
10. Requiring systemic treatment for an acute bacterial, viral, or fungal infection, or
having an unexplained fever (body temperature > 38.5℃) during screening prior to the
first dose.
11. Patients with moderate to large amount of body cavity effusion to be disposed of.
12. With a known history of psychiatric disorders or drug abuse that may affect
compliance.
13. Presence of any of the following conditions within 6 months prior to signing informed
consent: uncontrolled congestive heart failure (New York Heart Association class
II-IV), angina pectoris, myocardial infarction, stroke (except for lacunar
infarction), coronary/ peripheral artery bypass graft surgery, pulmonary embolism.
14. Arrhythmia unable to be controlled by drugs or sustained QTc(corrected QT interval )
interval prolongation, > 450 msec in males or > 470 msec in females.
15. Having participated in other clinical studies within 28 days prior to the first dose
of the study drug.
16. Pregnant or lactating women.
17. Women of childbearing potential, men of childbearing potential and their partners who
are unable to use effective and adequate dual contraception while receiving the study
drug and for 3 months after the end of the study.
18. Patient not suitable for participating in the study for any reason judged by the
investigator.
Additional exclusion criteria applicable to phase II trial period:
19. Patients with advanced biliary tract cancer previously treated with gemcitabine.
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Tianshu Liu, M.D., 8621-23193802, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT05357196
Organization ID
SCI-PT112-ONC-P2-002
Responsible Party
Sponsor
Study Sponsor
SciClone Pharmaceuticals
Study Sponsor
Tianshu Liu, M.D., Principal Investigator, Fudan University
Verification Date
April 2022