Overview

A Phase II Trial to Explore Niraparib and Anlotinib Maintenance Retreatment in Platinum-Sensitive Recurrent Ovarian Cancer Patients Previously Treated With PARPi

Status:
Not yet recruiting
Trial end date:
2024-09-01
Target enrollment:
0
Participant gender:
Female
Summary
This study will be an open-label, single-arm, prospective, exploratory phase II trial to investigate the efficacy and safety of niraparib maintenance retreatment in platinum- sensitive recurrent (PSR) epithelial ovarian cancer (EOC) patients (including patients with primary peritoneal and/or fallopian tube cancer).
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Peking Union Medical College Hospital
Collaborator:
Zai Lab (Shanghai) Co., Ltd.
Treatments:
Niraparib
Criteria
Inclusion Criteria:

- Provision of informed consent prior to any study specific procedures.

- Female patients ≥18 years of age, with histologically diagnosed platinum sensitive
recurrent high-grade serous or endometrioid epithelial ovarian cancer (EOC) (including
primary peritoneal and/or fallopian tube cancer).

- BRCA mutation status is known.

- Patients must have received one prior PARPi therapy, PARPi therapy includes any agent
(including niraparib) used in a maintenance setting and the duration of maintenance
treatment ≥6 months.

- Patients had received ≤3 lines of chemotherapy, the time between the penultimate line
of platinum-containing chemotherapy and the last platinum-containing chemotherapy was
> 6 months. For example, if a patient receives a non-platinum type of chemotherapy
between the penultimate line of platinum-containing chemotherapy and the last
platinum-containing chemotherapy, patient will be eligible if all the eligibility
criteria are met.

- The most recent round of platinum-containing chemotherapy should have included ≥4
cycles of treatment , in the opinion of the investigator, in response (partial or
complete radiological response) or may have no evidence of disease (if optimal
cytoreductive surgery was conducted prior to chemotherapy) .

- Patients must have either CA-125 in the normal range or CA-125 decrease by more than
90% during last line chemotherapy and that is stable for at least 7 days (ie, no
increase > 15% from nadir).

- Patients can have received bevacizumab during this course of treatment. Bevacizumab
use as part of an earlier line of therapy is permitted.

- Patients must be enrolled within 8 weeks of their last dose of chemotherapy (last dose
is the day of the last infusion).

- Patients must have a life expectancy ≥4 months.

- Eastern Cooperative Oncology Group performance status 0-2.

- Patients must have normal organ and bone marrow function, defined as follows: Absolute
neutrophil count ≥ 1,500/μL; Platelets ≥ 100,000/μL; Hemoglobin ≥ 10 g/dL; Serum
creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60
mL/min using the Cockcroft-Gault equation; Total bilirubin ≤ 1.5 x ULN OR direct
bilirubin ≤ 1 x ULN; Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x
ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN

- Negative serum or urine pregnancy test prior to receiving the first dose of study
treatment and willing to use adequate contraception to prevent pregnancy or must agree
to abstain from heterosexual activity throughout the study, starting with enrollment
through 90 days after the last dose of study treatment; or women of with no potential
fertility.

- Ability to comply with protocol.

- All of the adverse events caused by chemotherapy recovered to Common Terminology
Criteria Adverse Events (CTCAE) grade 1 or baseline, except for stable sensory
neuropathy or hair loss ≤ CTCAE grade 2.

Exclusion Criteria:

- Allergy to active or inactive ingredients of niraparib or drugs with similar chemical
structures.

- Allergy to active or inactive ingredients of anlotinib or drugs with similar chemical
structures.

- Active and uncontrollable brain metastasis or leptomeningeal metastasis. Patients with
spinal cord compression can still be considered if they have received targeted
treatment and have evidence of clinical stability of the disease for at least > 28
days (controlled brain metastasis must have received radiotherapy or chemotherapy at
least 1 month prior to study entry; patients may not have new symptoms related to
brain lesions or symptoms indicating disease progression and either take stable dose
of hormone or do not need to take hormone).

- Major surgery performed within 3 weeks before enrollment, or any surgical effects that
have not recovered from the surgery, or chemotherapy.

- Palliative radiotherapy encompassing >20% of the bone marrow within 1 week of the
first dose of study treatment.

- Any other malignant tumor exclude ovarian cancer has been diagnosed within 2 years
before enrollment (except for completely treated basal or squamous cell skin cancer).

- Current or previous myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).

- Other severe or uncontrolled diseases, including but not limited to: Uncontrollable
nausea and vomiting, inability to swallow study drug, and any gastrointestinal disease
that may interfere with the absorption and metabolism of the drug; Active viral
infections, such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus
and so on; Uncontrolled epileptic seizures, unstable spinal cord compression, superior
vena cava syndrome or other psychiatric disorders that may affect patients' informed
consent; Immunodeficiency (except for splenectomy), or other diseases that
investigators believe may expose patients to high-risk toxicity.

- Have the risk or tendency of bleeding and history of thrombosis: CTCAE grade 2
bleeding event occurred within 3 months prior to screening or CTCAE ≥ grade 3 bleeding
event occurred within 3 months prior to screening;

- Have history of gastrointestinal bleeding or confirmed bleeding tendency within 6
months prior to screening. e.g. esophageal varices with bleeding risk, local active
ulcer focus or fecal occult blood above ++.

- Have active bleeding or coagulation dysfunction, have bleeding risk or undergoing
thrombolytic or anticoagulant therapy: Need anticoagulant therapy with warfarin or
heparin; Need long-term anti-platelet therapy (e.g. aspirin, clopidogrel)

- Have occurred thrombus or embolism event in past 6 months, e.g. cerebral vascular
accident(including transient cerebral ischemic attack), pulmonary embolism.

- A history of severe cardiovascular disease: New York Heart Association (NYHA) grade
3/4 congestive heart failure (CHF); Unstable angina or newly diagnosed
angina/myocardial infarction within 12 months prior to screening; Cardiac arrhythmia
despite need medication (patients taking β-receptor blockers or digoxin can be
enrolled); CTCAE ≥ grade 2 valvular heart disease; Poorly controlled hypertension
(systolic pressure>150 mmHg or diastolic pressure>100 mmHg)

- The following laboratory indexed are abnormal: Hyponatremia (serum sodium < 130
mmol/L); baseline serum potassium < 3.5 mmol/L (potassium supplements can be used to
restore serum potassium above this before enrollment);Thyroid dysfunction and cannot
maintain normal despite medical treatment

- Previous/current diseases and treatment or abnormal laboratory indexed those interfere
with study result or participation of the whole study; or the investigator confirmed
not suitable for this trial; have platelet or red blood cell transfusion within 4
weeks prior to the first dose of study treatment.

- Patients must not be pregnant, breastfeeding, or expecting to conceive children, while
receiving study treatment.

- Corrected QT interval(QTc>450 milliseconds); if patients have QTc prolongation because
of cardiac pacemaker confirmed by investigator and no other cardiac disorder, whether
enrollment need further discussion with investigator.