Trial Title:
Surgery for Ovarian Cancer After PARPi Therapy in Precision
NCT ID:
NCT06602063
Condition:
Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Conditions: Keywords:
Ovarian cancer
Immune checkpoint inhibitor
Secondary cytoreduction
Biomarker-driven
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
surgery/chemotherapy
Description:
secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy
Arm group label:
compassionate use arm
Arm group label:
criteria-fulfilled arm
Intervention type:
Drug
Intervention name:
Sintilimab
Description:
Sintilimab will be administered at a fixed dose of 200 mg IV every 21 days. Treatment
will continue until disease progression confirmed by RECIST criteria v1.1, intolerable
toxicity or withdrawal of consent.
Arm group label:
compassionate use arm
Arm group label:
criteria-fulfilled arm
Summary:
This multicenter, biomarker-driven, patient-centric study aimed to evaluate the efficacy
of secondary cytoreduction followed by platinum-based chemotherapy in combination with
anti-PD1 therapy in patients with platinum-sensitive relapsed ovarian cancer (PSROC)
after previous PARP inhibitor maintenance therapy.
Detailed description:
There have been fewer effective treatments for patients with disease progression
occurring during or after PARP inhibitor maintenance therapy. The immune phenotype of
patients with relapsed ovarian cancer may correlate with their response to immunotherapy.
This multicenter, biomarker-driven, patient-centric study aimed to evaluate the efficacy
of secondary cytoreduction followed by platinum-based chemotherapy in combination with
anti-PD1 therapy in patients with platinum-sensitive relapsed ovarian cancer (PSROC)
after previous PARP inhibitor maintenance therapy. PD-L1 expression and CD8+
tumor-infiltrating T cell count (CD8+ TILs count) were evaluated as biomarkers using
archived or fresh tumor tissue samples in patients with BRCA1/2 wild type.
This study would be proceeded in two phases. The phase 1b single-arm study aimed to
evaluate the efficacy of Sintilimab in the treatment of BRCA wild type, PD-L1-positive,
CD8+ TILs-positive, patients with PSROC after previous PARPi maintenance therapy. The
patent-centric phase II study with three arms aimed to evaluate the efficacy of secondary
cytoreduction followed by platinum-based chemotherapy in combination with Sintilimab in
these patients. In arm 1 and 2, patients received secondary cytoreduction followed by
platinum-based chemotherapy in combination with Sintilimab. In arm 3, patients received
physician's therapy of choice.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Arm 1 (criteria-fulfilled, CF)
1. Age at recurrence ≥ 18 years, <80 years.
2. Patients with platinum-sensitive, first relapsed epithelial ovarian, primary
peritoneal, or fallopian tube cancer (EOC, PPC, FTC), which is defined as those
with treatment -free interval of 6 months or more.
3. Previous PARPi maintenance therapy with disease progression occurring at lease
3 months after the prior PARPi withdrawal.
4. BRCA1/2 wild type (both germline and somatic)
5. Homologous Recombination Deficiency (HRD) is available
6. Patients must provide archived or fresh tumor tissue samples for biomarker
detection.
7. PD-L1 positive (if either at least 1% of assessed tumour cells expressed
membranous PD-L1, at least 5% of immune cells within the tumour area expressed
PD-L1, or both) and number of intraepithelial CD8+ tumor-infiltrating
lymphocytes (TILs) per high-powered field ≥ 6.
8. Assessed by the experienced surgeons, complete resection of all recurrent
disease is possible (predicted by iMODEL score or by PET/CT).
9. ECOG performance status of 0 to 2
10. Adequate bone marrow, liver, and renal function to receive combined
immunotherapy
11. Written informed consent
- Arm 2 (compassionate use, CU), Similar to cohort 1, except for:
1. Previous PARPi maintenance therapy with disease progression occurring within 3
months after the prior PARPi withdrawal or during the PARPi maintenance
therapy.
2. PD-L1 positive or number of intraepithelial CD8+ TILs per high-powered field ≥
6.
- Arm 3 (real word) Patients who meet the inclusion criteria but refuse to participate
in the phase II CF and CU cohorts.
Exclusion Criteria:
1. Patients with borderline, low-grade tumors, clear cell carcinoma, as well as
non-epithelial tumors.
2. Patients with platinum-resistant or refractory diseases.
3. Lack of tumor samples (archived and/or recently obtained) for biomarker detection.
4. Previous administration of immunotherapy
5. Patients have been vaccinated with the live vaccine or received anti-tumor treatment
within 4 weeks before the first administration.
6. Synchronous or metachronous (within 5 years) malignancy, symptomatic or uncontrolled
visceral metastases that require simultaneous treatment, other than carcinoma in
situ or breast cancer (without any signs of relapse or activity).
7. Patients with parenchymal metastases and life-threatening complications in short
term.
8. Any other concurrent medical conditions contraindicating surgery, chemotherapy, or
immunotherapy that could compromise the adherence to the protocol.
9. Patients are known to be allergic to the active ingredients or excipients of
Sintilimab.
10. HRD status is not available.
11. Any medication induced considerable risk of surgery, e.g. estimated bleeding due to
oral anticoagulating agents or bevacizumab.
12. Patients for interval-debulking, or for second-look surgery, or palliative surgery
planned.
13. Impossible to assess the resectability of recurrent disease or evaluate the score.
Radiological signs suggesting complete resection is impossible.
Gender:
Female
Gender based:
Yes
Gender description:
participant eligibility is based on self-representation of gender identity
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhongshan Hospital Fudan University
Address:
City:
Shanghai
Country:
China
Contact:
Last name:
Tingyan Shi, MD, PHD
Email:
shi.tingyan@zs-hospital.sh.cn
Contact backup:
Last name:
Rongyu Zang, MD, PHD
Facility:
Name:
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Country:
China
Contact:
Last name:
Qinglei Gao, MD, PHD
Email:
gingleigao@hotmiail.com
Contact backup:
Last name:
Qinglei Gao, MD,PHD
Start date:
October 2024
Completion date:
September 2029
Lead sponsor:
Agency:
Shanghai Gynecologic Oncology Group
Agency class:
Other
Collaborator:
Agency:
Shanghai Zhongshan Hospital
Agency class:
Other
Collaborator:
Agency:
Tongji Hospital
Agency class:
Other
Source:
Shanghai Gynecologic Oncology Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06602063
