PD-1 Antibody Combined Neoadjuvant Chemotherapy for Ovarian Cancer

A Phase II Study of PD-1 Antibody Plus Neoadjuvant Chemotherapy for Advanced-stage Ovarian Cancer (Z2HOC-01)

The main purpose of this study is to validate the efficacy and safety of anti-PD-1 in combination with neoadjuvant chemotherapy in women with advanced ovarian cancer.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer; Neoadjuvant Chemotherapy; Anti-PD-1; Neoadjuvant Immunotherapy
• Intervention / Treatment: Drug: BGB-A317; Drug: albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5

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

Contacts and Locations

• Study Contact: Name: Zhigang Zhang, MD; Phone Number: +86057189713631; Email: zzg2011@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Zhigang Zhang, MD; Phone Number: +86057189713631; Email: zzg2011@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of ovary, fallopian tube, primary peritoneum (Non-mucinous adenocarcinoma)
2. Clinical stage IIIC/IV, and IIIC with Suidan CT ≥3 or Fagotti ≥8
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 ~ 2
4. Not received any immunotherapy before
5. Willing to participate in this study, and sign the informed consent.

Exclusion Criteria:

1. With other uncontrolled malignant tumors.
2. Any disease requiring systemic treatment with a corticosteroid (prednisone or equivalent daily dose of > 10mg) or other immunosuppressive agents during the 14 days prior to randomization.The use of topical substitute steroids (daily dose ≤10mg of prednisone or its equivalent) and prescription corticosteroids for short-term (≤7 days) prophylactic use or for the treatment of non-autoimmune conditions is permitted.Has any active autoimmune disease or a history of autoimmunity.
3. A history of active autoimmune disease or autoimmune disease that may recur.Enrolment was allowed for well-controlled type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, well-controlled celiac disease, skin conditions (such as vitiligo, psoriasis, or alopecia) that did not require systemic treatment, or conditions that were not expected to recede without an external cause.
4. A history of interstitial lung disease, non-infectious pneumonia, or poorly controlled diseases (including pulmonary fibrosis, acute lung disease, etc.).
5. Subjects with active hepatitis B (defined as positive hepatitis B virus surface antigen [HBsAg] test result and HBV-DNA test value higher than the upper limit of normal value in the laboratory of the research center) or hepatitis C (defined as positive hepatitis C virus surface antibody [HCSAB] test result and positive HCV-RNA test result).
6. Known human immunodeficiency virus (HIV) infection (known to be HIV positive).
7. Have received live vaccine within 30 days before the first administration.This includes but is not limited to the following: mumps, rubella, measles, varicella/herpes zoster (varicella), yellow fever, rabies, BCG and typhoid vaccines (inactivated virus vaccines are allowed).
8. With uncontrolled cardiac clinical symptoms or diseases.
9. Allergic to any drug in this program.
10. At the discretion of the Investigator, the subject has a history or current evidence of any disease, treatment or laboratory anomaly that may confuse the results, interfere with the participants' participation throughout the study, or is not in the best interest of the participants to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NIC; Neoadjuvant treatment BGB-A317 200mg q3 weeks (total 3 dosing) Chemotherapy regimen: albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5 q3 weeks (total 3 dosing); Interval debulking surgery and HIPEC; Adjuvant treatment Chemotherapy regimen: albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5, Bevacizumab 7.5mg/kg q3 weeks (total 3 dosing)	Drug: BGB-A317; PD-1 antibody，Tislelizumab (BGB-A317); Drug: albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5; albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5
Active Comparator: NC; Neoadjuvant treatment Chemotherapy regimen: albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5 q3 weeks (total 3 dosing); Interval debulking surgery and HIPEC; Adjuvant treatment Chemotherapy regimen: albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5, Bevacizumab 7.5mg/kg q3 weeks (total 3 dosing)	Drug: albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5; albumin-bound paclitaxel 260mg/m2 , Carboplatin AUC 5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS)	12 months progression-free survival rate will be estimated, and 95% confidence intervals will be calculated.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 rate	R0 rate of IDS(interval debulking surgery) after neoadjuvant chemotherapy(after the completion of 3rd cycle)	after interval debulking surgery for one week
CRR	CRR is defined as the percentage of the participants in the ITT population who have a Complete Response or Partial Response. The CRR will be assessed by a blind independent central reviewer per RECIST 1.1	3 months
PRR	At interval cytoreduction pathologic complete remission rate will be measured using RECIST and immune-related response criteria.	3 months
OS	OS is defined as the time from the date of randomization until death.	5 years
AEs	Proportion of patients with grade 3 or more treatment-related adverse events(except hematologic toxicity) graded by CTCAE v5 in neoadjuvant chemotherapy	3 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Jianwei Zhou, MD, Second Affiliated Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: March 23, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 25, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 1, 2021

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; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: Z2HOC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No