Niraparib Combined With Anlotinib In Homologous Recombination Repair (HRR) Gene-mutated Advanced Solid Tumors

Study Overview

Niraparib Combined With Anlotinib in Homologous Recombination Repair (HRR) Gene-mutated Advanced Solid Tumors

Homologous Recombination Repair (HRR) gene mutations can be detected in many solid tumors, patients with HRR gene mutations may benefit from PARP inhibitor. Antiangiogenic drugs can induce hypoxia and increase the sensitivity to PARP inhibitor. The combination of PARP inhibitor and antiangiogenic drug can play a synergistic anti-tumor role and achieve good efficacy in HRR gene-mutated tumors. The purpose of the study is to determine the dose limiting toxicity (DLT) and maximum tolerable dose (MTD) of Niraparib plus Anlotinib in HRR gene-mutated advanced solid tumors, and evaluate the safety and effectiveness of this combination therapy preliminarily.

This is a single-arm, single-center, phase I study to investigate the DLT and MDT, safety and efficacy of Niraparib combined with Anlotinib in the treatment of advanced solid tumors with HRR gene mutations. In this study, 52 histological or cytological diagnosis, previous treatment failure patients of HER2 negative breast cancer, cholangiocarcinoma, gastric adenocarcinoma and pancreatic cancer are included and receive Niraparib combined with Anlotinib. Patients are required to carry pathogenic or suspected pathogenic gBRCA or sBRCA mutations, or HRR gene mutations defined by the inclusion criteria. The study will be divided into two phase. The first phase will include 6-12 patients on a 21-day cycle to determine the DLT and MTD. In the second phase, 40 patients will be included to treated with Niraparib plus Anlotinib until disease progression or intolerable toxicity or withdrawal of the trial.

HER2-negative Breast Cancer
Gastric Adenocarcinoma
Cholangiocarcinoma
Pancreatic Cancer

DRUG: Niraparib
DRUG: Anlotinib

ZL-2306-912 ALTER-OC-02

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-02-18	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2021-02-18
First Submitted that Met QC Criteria 2021-02-18	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2021-02-21
First Posted (ACTUAL) 2021-02-21	Results First Posted N/A	Last Verified 2021-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment group Niraparib-Anlotinib combination therapy	DRUG: Niraparib Niraparib 100mg or 200mg, PO, qd，d1-d21 DRUG: Anlotinib Anlotinib 12mg, PO, qd，d1-d14

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment group

Niraparib-Anlotinib combination therapy

DRUG: Niraparib

Niraparib 100mg or 200mg, PO, qd，d1-d21

DRUG: Anlotinib

Anlotinib 12mg, PO, qd，d1-d14

Primary Outcome Measures	Measure Description	Time Frame
Dose limiting toxicity (DLT) and maximum tolerated dose (MTD)		4 weeks

Secondary Outcome Measures	Measure Description	Time Frame
The frequency and severity of adverse events	The frequency and severity of adverse events and toxicity based upon NCI CTCAE version 5.0 during subjects receiving the treatment	Baseline through 1 year
Objective Response Rate (ORR)	The ORR is a combination of CR (the target lesion completely disappeared over 4 weeks) and PR (Target lesions were reduced by more than 30% for more than 4 weeks).	at 6 months
Progression-free survival (PFS)	PFS is defined as the time from enrollment to first documentation of tumor progression, or to death due to any cause in the absence of previous documentation of objective tumor progression.	at 6 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Jiayang Zhang, M.D.

Phone Number: +86-010-88196380

Email: jiayangzhang2015@qq.com

Study Contact Backup

Name: Anqiang Wang, M.D.

Phone Number: +86-010-88196970

Email: wanganqiang0902@163.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Subjects understand the trial process, sign informed consent, agree to participate in the study, and have the ability to follow the protocol;
18 ~ 70 years old
HER2 negative breast cancer, cholangiocarcinoma, gastric adenocarcinoma and pancreatic cancer confirmed by histology or cytology meet any of the following conditions: first line treatment failure of HER2 negative breast cancer; first line treatment failure of cholangiocarcinoma; second line treatment failure of gastric adenocarcinoma; first line treatment failure of pancreatic cancer
At least one measurable target lesion that meet RECIST 1.1 criteria
Can provide paraffin-embedded tumor tissue samples or plasma samples for HRR gene detection
Carry pathogenic or suspected pathogenic germline or somatic HRR gene mutations, HRR genes include BRCA1, BRCA2, ATM, ATR, BAP1, BRIP1, CHEK2, FANCA, PALB2 and RAD51, mutations in other HRR genes should be evaluated by researchers and the pathogenicity should be supported by published literature or clinical studies.
ECOG physical status score is 0-1
Life expectancy > 6 months
Good organ function, including: Neutrophil count >= 1500 / μL; Platelets >= 100,000 / μL; Hemoglobin >= 10g / dL; Serum creatinine <= 1.5 times the upper limit of normal value, or creatinine clearance >= 60mL / min (calculated according to Cockcroft-Gault formula); Total bilirubin <= 1.5 times the upper limit of normal value or direct bilirubin <= 1.0 times the upper limit of normal value; AST and ALT <= 2.5 times the upper limit of normal value. When liver metastases are present, it must be <= 5 times the upper limit of normal value
The toxic side effects of any previous chemotherapy have recovered to <= CTCAE level 1 or baseline levels, except for sensory neuropathy or hair loss with stable symptoms <= CTCAE level 2

People who are known to be allergic to Niraparib or Anlotinib (or active or inactive ingredients of drugs with similar chemical structure)
Symptomatic, uncontrolled brain or pia mater metastases
Underwent major surgery within 3 weeks before the study began or has not recovered after surgery
Received palliative radiotherapy of > 20% bone marrow 1 week before enrollment
Have invasive cancer other than ovarian cancer (except fully treated basal or squamous cell skin cancer) within 2 years before enrollment
Patients with tumor invasion of large vessels
Previous or currently diagnosed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
Severe or uncontrolled diseases, including but not limited to: uncontrollable nausea and vomiting, inability to swallow or gastrointestinal diseases that may interfere with drug absorption and metabolism; active viral infections; mental illnesses that affect patients' signed informed consent History of bleeding tendency and thrombosis; history of severe cardiovascular disease
Laboratory abnormalities: hyponatremia; hypokalemia; uncontrollable nail function abnormalities
Receive platelet or red blood cell transfusions within 4 weeks
Patients who are pregnant or nursing, or who plan to become pregnant during study treatment
Have previously received any PARP inhibitor or Anlotinib treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Huiping Li, M.D., Peking University Cancer Hospital & Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record