HER2-negative Breast CancerPhase 1NCT04764084
Niraparib Combined With Anlotinib in Homologous Recombination Repair (HRR) Gene-mutated Advanced Solid Tumors
A Phase 1 study testing Niraparib and Anlotinib in people with HER2-negative Breast Cancer and Gastric Adenocarcinoma, run by Peking University Cancer Hospital & Institute at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HER2-negative Breast Cancer, Gastric Adenocarcinoma, Cholangiocarcinoma
- What is being tested?
- Niraparib and Anlotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2021to 28 Feb 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Huiping Li, M.D., +86-010-88196739, huipingli2012@hotmail.com
Jiafu Ji, M.D., +86-010-88122437, jijiafu@hsc.pku.edu.cn
About this study
Official title: 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.
Read the 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.
- Conditions
- HER2-negative Breast Cancer, Gastric Adenocarcinoma, Cholangiocarcinoma, Pancreatic Cancer
- Keywords
- Niraprib, Anlotinib, Homologous Recombination Repair, breast cancer, gastric Adenocarcinoma, cholangiocarcinoma, pancreatic cancer
- Medical subject headings
- Cholangiocarcinoma, Pancreatic Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
Niraparib 100mg or 200mg, PO, qd，d1-d21
AnlotinibDrug
Anlotinib 12mg, PO, qd，d1-d14
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | Niraparib-Anlotinib combination therapy Receives: Drug: Niraparib; Drug: Anlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT) and maximum tolerated dose (MTD)
Measured: 4 weeks
Secondary outcomes (3)
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
Measured: 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).
Measured: 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.
Measured: at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start1 Apr 2021 (estimated)
- Primary completion1 Nov 2021 (estimated)
- Study completion28 Feb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-negative Breast CancerStudies of the same condition, open and under way.
- More trials run by Peking University Cancer Hospital & InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li Huiping, Peking University Cancer Hospital & Institute
- Investigators
- Huiping Li, M.D., Principal investigator, Peking University Cancer Hospital & InstituteJiafu Ji, M.D., Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04764084
- Sponsor's protocol ID
- ZL-2306-912 ALTER-OC-02
- Status last verified
- Feb 2021
- First submitted
- 18 Feb 2021
- Last updated
- 21 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Within six months after the trial complete, study protocol, informed consent form and clinical study report will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Single Center, Phase I Trial of Niraparib Plus Anlotinib in Advanced Solid Tumors With Homologous Recombination Repair (HRR) Gene Mutations
- ClinicalTrials.gov ID
- NCT04764084
- Acronym / sponsor ID
- ZL-2306-912 ALTER-OC-02
- Conditions
- HER2-negative Breast Cancer, Gastric Adenocarcinoma, Cholangiocarcinoma, Pancreatic Cancer
- Keywords
- Niraprib, Anlotinib, Homologous Recombination Repair, breast cancer, gastric Adenocarcinoma, cholangiocarcinoma, pancreatic cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Peking University Cancer Hospital & InstituteUniversity, hospital or other
- Study start
- 1 Apr 2021 (estimated)
- Primary completion
- 1 Nov 2021 (estimated)
- Study completion
- 28 Feb 2023 (estimated)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: Niraparib, Drug: AnlotinibNiraparib-Anlotinib combination therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZejulaNiraparib 100mg or 200mg, PO, qd，d1-d21 | Drug | Treatment group |
| AnlotinibAnlotinib 12mg, PO, qd，d1-d14 | Drug | Treatment group |
Primary outcome
Dose limiting toxicity (DLT) and maximum tolerated dose (MTD)
Time frame: 4 weeks
3 secondary outcomes
The frequency and severity of adverse events
Time frame: Baseline through 1 year
Objective Response Rate (ORR)
Time frame: at 6 months
Progression-free survival (PFS)
Time frame: at 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
- Individual participant dataSharing planned: Yes. Within six months after the trial complete, study protocol, informed consent form and clinical study report will be shared.
Related trials for HER2-negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Recruiting
Short-Term Reduced Dietary Protein in ER+/HER2- Breast Cancer Patients During Neoadjuvant Chemotherapy
Breast Cancer, Hormone Receptor Positive / HER2-negative Breast Cancer
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
RecruitingPhase 3
Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
RecruitingObservational study
A Study to Assess Treatment Patterns and Treatment Adherence in Early HER2-positive Breast Cancer Participants After Treatment Decentralization
Early-stage HER2+ Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Huiping Li, M.D. principal investigator
Peking University Cancer Hospital & Institute
Jiafu Ji, M.D. principal investigator
Peking University Cancer Hospital & Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Niraparib and Anlotinib in people with HER2-negative Breast Cancer and Gastric Adenocarcinoma, run by Peking University Cancer Hospital & Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jiayang Zhang, M.D. (+86-010-88196380, jiayangzhang2015@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (DLT) and maximum tolerated dose (MTD) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.