Anlotinib and Niraparib Dual Therapy Evaluation in Platinum-resistant Recurrent Ovarian Cancer (ANNIE)

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)

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).

Study Overview

• Status: Unknown
• Conditions: Platinum-resistant Ovarian Cancer
• Intervention / Treatment: Drug: Niraparib; Drug: Anlotinib

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: guochen liu, Dr; Phone Number: +86 13570314425; Email: liugch@sysucc.org.cn
      • Sub-Investigator: guochen liu, Dr
      • Principal Investigator: Jihong Liu, Pro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Niraparib 300mg(Body Weigh ≥77 kg)/200mg (Body Weigh <77 kg) po QD day1~21, Anlotinib 12mg po QD day1~14. Starting dose of anlotinib changed to 10mg from 2020-11-13.	Drug: Niraparib; Niraparib 300mg(Body Weigh ≥77 kg)/200mg (Body Weigh <77 kg) po QD day1~21, Anlotinib 12mg po QD day1~14; Drug: Anlotinib; Anlotinib 12mg po QD day1~14. Starting dose of anlotinib changed to 10mg from 2020-11-13.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The primary objective of this study is to determine the preliminary efficacy of administration of niraparib in combination with anlotinib in the treatment of platinum-resistant recurrent ovarian cancer, as measured by the objective response rate (ORR), which 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 study treatment.	Baseline through 1 year
Progression-free survival	Progression-free survival 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
Objective tumor response	The total proportion of subjects who have an objective tumor reponse (CR + PR) using the RECIST criteria.	at 6 months

Collaborators and Investigators

• Sponsor: Jihong Liu

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: May 1, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 6, 2020

Study Record Updates

• Last Update Posted (Actual): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 23, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Niraparib
• Other Study ID Numbers: 2019-FXY-357

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: Within six months after the trial complete
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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