Treatment of Carrying TP53 Harmful Mutations

NCT03645200 | Unknown Phase 1

• 1 other identifier: TP53MuToma
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Assessment of the safety and tolerability of Fluzoparib combined with Apatinib in the treatment of advanced refractory solid tumors with TP53 harmful mutations.

Conditions

Advanced Cancer

Keywords

TP53; Solid tumor; Fluzoparib; Apatinib

Outcome Measures

Primary Outcomes (1)

• Dosage (provide right dosage for II phase clinical trial)

  provide right dosage for II phase clinical trial

  12 months

Secondary Outcomes (2)

• ORR: objective response rate

  12 months

• DCR: disease control rate

  12 months

Study Arms (1)

Fluzoparib combined with Apatinib

EXPERIMENTAL

Fluzoparib in the initial dose of 40mg.bid started into the group of participants, group A combined with a fixed dose of Apatinib 250mg.qd for treatment, followed by the 40mg.bid, 60mg.bid, 80mg.bid, 100mg.bid dose increase. Fluzoparib in the initial dose of 40mg.bid started into the group of participants, Group B was treated with a fixed dose of Apatinib 500mg.qd, followed by an increase in doses of 40mg.bid, 60mg.bid, 80mg.bid, 100mg.bid .

Drug: Fluzoparib combined with Apatinib

Interventions

Fluzoparib combined with Apatinib DRUG

Fluzoparib : 40mg.bid, morning and evening each time, interval of 12 hours or so, the first oral administration 72 hours later Apatinib : 250mg or 500mg take one day, 72 hours later, the continuous drug delivery phase (B-C1D1) was entered into the Fluzoparib, that is, the Fluzoparib capsule with 40mg.bid, every morning and evening, each time, interval of 12 hours, the Apatinib tablets daily with the Fluzoparib capsule with the same service, fixed doses of 250mg or 500mg, daily. Continuous drug delivery for 28 days for one cycle

Also known as: Apatinib mesylate tablets

Fluzoparib combined with Apatinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age is 18≥years ≤70 years .
• ECOG body State is 0\~1 score.
• The estimated survival period are greater than 3 months .
• Histologic or cytological diagnosis of advanced refractory tumors that are ineffective or without standard treatment by standard multi-line therapy. The definition of treatment invalidity: progression of disease after multiple line therapy.
• With the relevant qualification agencies NGS (second generation sequencing) report, and the molecular Oncology Expert Committee identified TP53 as the main harmful mutation.
• The patient has at least one measurable lesion that can be assessed by CT or MRI (RECIST 1.1).
• Previous treatment of any anti-tumor therapy (including radiotherapy, chemotherapy, hormone therapy, surgery, or molecular targeting therapy) ended with the Thou Yan ≥4 weeks (to the first medication) in this trial.
• Urine routine display urine protein \<2+, if urine protein qualitative ≥2+, should accept 24 hour urine protein quantitative detection, ≤ 1g can be entered into a group.
• Good organ function level ( no blood transfusion, no use of G-CSF in the first 7 days of screening ; no drug correction;7 days without loss ALB):ANC≥ 1.5x109/L;WBC≥ 3x109 /L;PLT≥80x109/L ;Hb≥90g/l; TBIL≤1.5xULN;ALT and AST≤2.5xULN; ALB≥29g/l ;BUN and Cr ≤1. 5xULN ;LVEF ≥50%;Fridericia method to correct QT Inter-period (QTcF ) Male \<450 ms , Women \<470 ms .
• Women of childbearing age are required to take effective contraceptive measures at least 8 weeks after taking part in the study and after the last drug delivery .
• Can follow the test plan according to the judgment of the investigator.
• Volunteer to participate in this clinical trial, have the ability to understand the research requirements, can give written informed consent.

You may not qualify if:

• Anticancer drugs, including Fluzoparib that used or were using PARP as a target.
• Antineoplastic agents used or using VEGFR targets, including Apatinib.
• As a participant in the clinical trial, and the signing of the informed consent of the last clinical trial at the end of the interval of less than days.
• Has a blood system-related tumor.
• Receive any anti-tumor treatment (including radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeting therapy) within 4 weeks before delivery;
• Double phosphate drug treatment was received in the first 4 weeks of the drug delivery;
• There is a CTCAE grade II toxicity caused by previous treatment.
• Hypertension is not controlled (systolic pressure is greater than 150mmHg, or diastolic pressure is greater than 90 mmHg); or a history of congestive heart failure (American Heart Association heart function grade ≥2 Level).
• Clinically significant heart disease, including but not limited to: congestive heart failure, symptomatic coronary artery disease, arrhythmia, myocardial infarction, QTc period ≥470ms.
• Intestinal obstruction or CTCAE 3 or 4 upper digestive tract bleeding in the first 4 weeks before the drug delivery.
• Inability to swallow, inflammatory bowel disease or uncontrollable nausea, vomiting, diarrhea or other gastrointestinal disorders that seriously affect drug use and absorption.
• The tumor metastasis of central nervous system was diagnosed by the researchers.
• A history of severe venous thrombosis or pulmonary embolism.
• There is a third interstitial fluid (such as large pleural effusion and ascites) that cannot be controlled by drainage or other means.
• There is still an electrolyte disorder that cannot be corrected when the group is given a drug.

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

Tianjin Medical Unversity Second Hospital

Tianjin, Tianjin Municipality, 300200, China

Location

MeSH Terms

Interventions

apatinib

Study Officials

• Haitao Wang, Ph.D

  Tianjin Medical University Second Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haitao Wang, Ph.D

CONTACT

+86-022-88326385; peterrock2000@126.com

Study Design

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

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 24, 2018
• Study Start: July 1, 2019
• Primary Completion: December 1, 2019
• Study Completion: June 1, 2020
• Last Updated: April 25, 2019

Record last verified: 2018-08

Locations

CN (1)