Clinical trial NCT05152797: Efficacy and Safety of TILs in Treatment of Patients With Advanced or Metastatic Refractory Gynecological Cancer
Official title: Efficacy and Safety of Autologous Tumor-infiltrating Lymphocytes in Treatment of Patients With Advanced or Metastatic Refractory Gynecological Cancer: a Prospective Multicenter One-arm Phase Ⅱ Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Tumor Infiltrating Lymphocytes
Lead sponsor: Women's Hospital School Of Medicine Zhejiang University
Sponsor class: OTHER
Collaborators: name: Tongji Hospital
name: Qilu Hospital of Shandong University
name: Sun Yat-sen University
First posted: 2021-12-10
Enrollment: 91
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Prospective, multicenter, single-arm, open label, interventional basket trial to evaluate autologous tumor-infiltrating lymphocytes (TILs) infusion followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparation for the treatment of patients with advanced or metastatic refractory gynecological cancer including cervical, ovarian, endometrial and breast carcinoma.

Detailed description: Autologous tumor-infiltrating lymphocytes (TILs) infusion is highly personalized cancer immunotherapy with strong anti-tumor efficacy and tumor specificity. TILs were extracted from autologous fresh tumor tissues, and after ex vivo stimulation, activation and extensive expansion, are reinfused to patients. TIL-based therapies have only been offered in small phase I/II studies in a few centers and revealed a high objective response rate (ORR) in the treatment of metastatic, recurrent or advanced melanoma, non-small cell long carcinoma and cervical carcinoma. However, the efficacy of TIL-based therapies still needs more clinical trials to prove. In this proposal, a one-arm, open, multicenter, phaseⅠ/Ⅱ trial was designed to evaluate the efficacy and safety of autologous tumor-infiltrating lymphocytes in treatment of patients with advanced or metastatic refractory gynecological cancer including cervical, ovarian, endometrial and breast carcinoma.

Eligibility criteria: Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria: Signed informed consent must be obtained prior to participation in the study.

* Aged 18-75 years old at the time of consent
* Participants are diagnosed with advanced or metastatic cervical cancer, ovarian cancer, endometrial cancer or breast cancer with radiology and pathology confirmation.
* Failure of two or more Lines of Chemotherapy, or not amenable to curative treatment.
* At least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post-resection to extract TIL
* At least one measurable target lesion, that can be accurately measured in at least one dimension with longest diameter ≥20 mm, as defined by RECIST v1.1
* All the chemotherapy or radiotherapy targeting the malignant tumors must be discontinued at least 28 days prior to the tumor resection.
* No serious abnormality of complete blood count and Cardiac, Liver, and Kidney function

Exclusion Criteria:

* Participants who have received organ transplantation or prior cell transfer therapy
* Any active autoimmune disease or history of autoimmune disease, or history of primary immunodeficiency.
* Patients who are taking systemic steroid therapy
* Patients with confirmed HIV infection, or other uncontrolled active viral infections, or serious system infections
* Patients with serious complications of heart, lung, liver, kidney, not suitable for enrollment.
* Patients with suspicious or confirmed brain metastases of any size and any number.
* Suffered from any other malignancy within 5 years (except for fully treated in situ malignant such as breast cancer, bladder cancer, cutaneous basal cell carcinoma or squamous cell carcinoma)
* Patients who are pregnant or breastfeeding
* Any other conditions judged by the researcher will significantly increase the risk of participation.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Up to 6 months
Secondary outcomes:
measure: Disease Control Rate
timeFrame: Up to 60 months
measure: Progression-Free Survival
timeFrame: Up to 60 months
measure: Overall Survival
timeFrame: Up to 60 months
measure: Adverse Events
timeFrame: Up to 60 months
Other outcomes:
Locations:
Study officials:
affiliation: Women's Hospital School Of Medicine Zhejiang University
name: Hui Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: