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

NCT04764084 | Unknown Phase 1

• 1 other identifier: ZL-2306-912 ALTER-OC-02
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HER2-negative Breast Cancer; Gastric Adenocarcinoma; Cholangiocarcinoma; Pancreatic Cancer

Keywords

Niraprib; Anlotinib; Homologous Recombination Repair; breast cancer; gastric Adenocarcinoma; cholangiocarcinoma; pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT) and maximum tolerated dose (MTD)

  4 weeks

Secondary Outcomes (3)

• The frequency and severity of adverse events

  Baseline through 1 year

• Objective Response Rate (ORR)

  at 6 months

• Progression-free survival (PFS)

  at 6 months

Study Arms (1)

Treatment group

EXPERIMENTAL

Niraparib-Anlotinib combination therapy

Drug: Niraparib; Drug: Anlotinib

Interventions

Niraparib DRUG

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

Also known as: Zejula

Treatment group

Anlotinib DRUG

Anlotinib 12mg, PO, qd，d1-d14

Treatment group

Eligibility Criteria

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

You may qualify if:

• Subjects understand the trial process, sign informed consent, agree to participate in the study, and have the ability to follow the protocol;
• \~ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Pancreatic Neoplasms; Breast Neoplasms

Interventions

niraparib; anlotinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Huiping Li, M.D.

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

• Jiafu Ji, M.D.

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiayang Zhang, M.D.

CONTACT

+86-010-88196380; jiayangzhang2015@qq.com

Anqiang Wang, M.D.

CONTACT

+86-010-88196970; wanganqiang0902@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Breast Oncology

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: February 21, 2021
• Study Start: April 1, 2021
• Primary Completion: November 1, 2021
• Study Completion: February 28, 2023
• Last Updated: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Within six months after the trial complete
• Access Criteria: Publication

Locations

CN (1)