A Phase I Trial of SHR3162 in Subjects With Advanced Solid Tumors

NCT02759666 | Completed Phase 1

• 1 other identifier: SHR3162-002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, multicenter, non-randomized, dose-escalation phase 1 trial to evaluate the safety and tolerability of SHR3162 in participants with advanced solid tumors.

Conditions

Neoplasm; Solid Tumors

Keywords

PARP; advanced solid tumor

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  MTD will be defined as the maximum dose level at which no more than one 1 of 3 participants experience a dose-limiting toxicity (DLT) within the first 4 weeks of multiple dosing

  4 weeks

Secondary Outcomes (6)

• Number of participants with treatment-emergent adverse events

  24 months

• Peak plasma concentration (Cmax)

  4 weeks

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

  4 weeks

• T1/2 (half-life)

  4 weeks

• Clearance (CL)

  4 weeks

Study Arms (1)

SHR3162

EXPERIMENTAL

3 to 6 participants (traditional "3+3" design) will be enrolled in 6 dose levels. SHR3162 was administered once daily in dose levels 1 and 2 and will be administered twice daily in dose levels 3 to 6.

Drug: SHR3162

Interventions

SHR3162 DRUG

SHR3162 capsule(s) is administered orally QD.

Also known as: Fluzoparib

SHR3162

Eligibility Criteria

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

You may qualify if:

• Males and/or females over age 18.
• Ability to understand the purposes and risks of the trial and his/her signed informed consent form approved by Human Research Ethics Committee (HREC) of the trial site was obtained before the entering the trial.
• Histologically or cytologically confirmed advanced or metastatic solid tumor for which no established standard therapy is available.
• At least one measurable lesion by CT or MRI according to RECIST Version 1.1, which is not in irradiated area (only for expansion phase).
• Recovered from toxicities of prior anti-cancer treatment to Grade 1 or less (in case of alopecia, Grade 2 is acceptable).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 3 months.
• Acceptable liver function defined below:
• Total bilirubin ≤1.5 times upper limit of normal (ULN);
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times ULN; however, ≤5 times ULN in a participant who has liver metastases or is treated with biliary drainage
• Acceptable renal function defined below:
• Serum creatinine ≤1.5 times ULN or calculated creatinine clearance (by the Cockcroft-Gault formula) ≥60 mL/minutes
• Acceptable coagulation status defined below:
• Prothrombin time \<1.3 times ULN
• Partial thrombin time \<1.3 times ULN

You may not qualify if:

• Hematologic malignancies.
• Cardiac disease with New York Heart Association (NYHA) Class III or IV, including congestive heart failure, myocardial infarction within 6 months prior to the trial entry, unstable arrhythmia, or symptomatic peripheral arterial vascular disease.
• Previously treated malignancies other than the current disease, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years at the trial entry.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Major surgery, other than diagnostic surgery, within 4 weeks prior to the trial entry, without complete recovery.
• Percutaneous coronary intervention conducted within 6 months prior to the trial entry for cardiac infarction or angina pectoris.
• Seizure disorders requiring anticonvulsant therapy.
• Taking a medication that prolongs QT interval and has a risk of Torsade de Pointes, or a history of long QT syndrome.
• Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
• Anti-cancer treatment with radiation therapy, surgery, chemotherapy, targeted therapies (erlotinib, lapatinib, etc.), hormone therapy, or immunotherapy within 4 weeks (6 weeks for nitrosoureas or Mitomycin C) prior to trial entry, and ever use PARP inhibitor.
• Participation in an investigational drug or device trial within 4 weeks prior to the trial entry.
• Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
• Recent venous thrombosis (including deep vein thrombosis or pulmonary embolism within 1 year of study).
• History of upper gastrointestinal hemorrhage, peptic ulcer disease, or bleeding diathesis.
• Subject is pregnant (positive serum beta human chorionic gonadotropin \[β-HCG\] test at screening) or is currently breast-feeding, their partner anticipates becoming pregnant/impregnating during the trial or within 6 months after receiving the last dose of trial treatment.

Sponsors & Collaborators

• Atridia Pty Ltd.: lead

Study Sites (3)

Border Medical Oncology

Albury, New South Wales, 2640, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Linear

Melbourne, Australia

Location

MeSH Terms

Conditions

Neoplasms

Interventions

fluzoparib

Study Design

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

Study Record Dates

• First Submitted: April 29, 2016
• First Posted: May 3, 2016
• Study Start: June 1, 2016
• Primary Completion: March 8, 2019
• Study Completion: April 26, 2019
• Last Updated: September 19, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)