Clinical trial NCT04376073: Anlotinib and Niraparib Dual Therapy Evaluation in Platinum-resistant Recurrent Ovarian Cancer
Official title: An Open-label, Single Arm, Phase II Trial of Niraparib in Combination With Anlotinib in Patients With Platinum-resistant Recurrent Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer (Ovarian Cancer)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Platinum-resistant Ovarian Cancer
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2020-05-06
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: At present, the standard treatment for platinum-resistant ovarian cancer patients is platinum-free chemotherapy, with poor efficacy and tolerance. The combination of anti-angiogenic drugs and PARPi can play a synergistic anti-tumor role and achieve good efficacy in platinum-sensitive recurrent ovarian cancer. This study intends to explore the safety and effectiveness of anlotinib and niraparib dual therapy in patients with platinum-resistant recurrent ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (ovarian cancer).

Detailed description: The present study is an open, single-center, prospective, single-arm phase II study to investigate the efficacy and safety of nilapalil combined with anrotidine in the treatment of platinum-resistant recurrent ovarian cancer. In this study, 40 histopathologically diagnosed patients with high-grade serous ovarian, fallopian tube and primary peritoneal cancer were treated with neelapalil plus anrotinib in patients who underwent first-line chemotherapy or above and had a recurrence of platinum-resistant chemotherapy (the time of tumor progression of the last platinum-containing chemotherapy \< 6 months). The study will be divided into two phases. The first phase will include six patients on a 21-day cycle (nierapalil 200mg QD\*21; Anrotidine 12mg qd d1-14, d15-21 suspension), all subsequent patients were enrolled if no more than dose-restricted toxic event occurred within a cycle, and the combination treatment was continued until the disease progressed or the toxicity was intolerable.

Eligibility criteria: Inclusion Criteria:

* 1. Subjects understand the trial process, sign informed consent, agree to participate in the study, and have the ability to follow the protocol; 2. 18 \~ 70 years old (inclusive), female; 3. Histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer; 4. Subjects were initially treated with platinum, and the disease recurrence occurred within 6 months after the end of the previous platinum-containing chemotherapy, that is, platinum resistance relapsed; 5. Life expectancy \> 16 weeks; 6. Patient's ECOG physical status score is 0-1; 7. Subject agrees to take blood samples for gBRCA mutations; 8. Can provide formalin-fixed, paraffin-embedded tumor tissue samples for sBRCA and homologous recombination repair-related genes detection (optional); 9. Good organ function, including:
* Neutrophil count \>= 1500 / μL;
* Platelets \>= 100,000 / μL;
* Hemoglobin \>= 9g / 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.

  10. 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:

1. People who are known to be allergic to Niraparib or Anlotinib (or active or inactive ingredients of drugs with similar chemical structure);
2. Symptomatic, uncontrolled brain or pia mater metastases;
3. Underwent major surgery within 3 weeks before the study began or has not recovered after surgery;
4. Received palliative radiotherapy of \> 20% bone marrow 1 week before enrollment;
5. Have invasive cancer other than ovarian cancer (except fully treated basal or squamous cell skin cancer) within 2 years before enrollment;
6. Patients with central lung squamous cell carcinoma or at risk for large hemoptysis;
7. Previous or currently diagnosed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML);
8. 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;
9. Laboratory abnormalities: hyponatremia; hypokalemia; uncontrollable nail function abnormalities;
10. Receive platelet or red blood cell transfusions within 4 weeks;
11. Patients who are pregnant or nursing, or who plan to become pregnant during study treatment;
12. Have previously received any PARP inhibitor treatment.

Primary outcomes:
measure: Objective Response Rate
timeFrame: at 6 months
Secondary outcomes:
measure: The frequency and severity of adverse events
timeFrame: Baseline through 1 year
measure: Progression-free survival
timeFrame: at 6 months
measure: Objective tumor response
timeFrame: at 6 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
Study officials:
References: