Clinical trial NCT06602063: Surgery for Ovarian Cancer After PARPi Therapy in Precision
Official title: Surgery with ICBs in BRCAwt, CD8+ TILs, 1st Relapsed Ovarian Cancer After PARPi Maintenance Therapy: a Pilot Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Keywords: Ovarian cancer
Immune checkpoint inhibitor
Secondary cytoreduction
Biomarker-driven
Lead sponsor: Shanghai Gynecologic Oncology Group
Sponsor class: OTHER_GOV
Collaborators: name: Shanghai Zhongshan Hospital
name: Tongji Hospital
First posted: 2024-09-19
Enrollment: 33
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Primary outcomes:
measure: Progression-free survival in CF arm
timeFrame: Up to 3 years
measure: 3-years Overall Survival Rate in CF arm
timeFrame: Up to 3 years
Secondary outcomes:
measure: Overall survival in CF arm
timeFrame: Up to 3 years
measure: TFST in CF arm
timeFrame: Up to 3 years
measure: TSST in CF arm
timeFrame: Up to 3 years
measure: Post-operative complications in CF and CU arms
timeFrame: Up to 1 months
measure: Quality of life assessments in CF arm using EORTC QLQ-C30
timeFrame: Up to 3 years
measure: Quality of life assessments in CF arm using FACT-O
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Study officials:
References: