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

February 18, 2021 updated by: Li Huiping, Peking University Cancer Hospital & Institute

A Single Arm, Single Center, Phase I Trial of Niraparib Plus Anlotinib in Advanced Solid Tumors With Homologous Recombination Repair (HRR) Gene Mutations

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

52

Phase

  • Phase 1

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

Study Contact Backup

Study Locations

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.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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
Other Names:
  • Zejula
Drug: Anlotinib
Anlotinib 12mg, PO, qd，d1-d14

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The frequency and severity of adverse events
Time Frame: Baseline through 1 year
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)
Time Frame: at 6 months
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)
Time Frame: at 6 months
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

Collaborators and Investigators

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

Sponsor

Peking University Cancer Hospital & Institute

Investigators

  • Principal Investigator: Huiping Li, M.D., Peking University Cancer Hospital & Institute

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 Major Dates

Study Start (Anticipated)

April 1, 2021

Primary Completion (Anticipated)

November 1, 2021

Study Completion (Anticipated)

February 28, 2023

Study Registration Dates

First Submitted

February 18, 2021

First Submitted That Met QC Criteria

February 18, 2021

First Posted (Actual)

February 21, 2021

Study Record Updates

Last Update Posted (Actual)

February 21, 2021

Last Update Submitted That Met QC Criteria

February 18, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZL-2306-912 ALTER-OC-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Within six months after the trial complete, study protocol, informed consent form and clinical study report will be shared.

IPD Sharing Time Frame

Within six months after the trial complete

IPD Sharing Access Criteria

Publication

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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