Phase Ib Study To Assess The Feasibility And Safety Of Adoptive Transfer Of Autologous Tumor-Infiltrating Lymphocytes In Advanced Solid Tumors

Centre Hospitalier Universitaire Vaudois1 site in 1 country6 target enrollmentSeptember 1, 2019

ConditionsSolid Tumor, Adult

InterventionsTIL Cyclophosphamide Fludarabine Interleukin-2 Radiotherapy

DrugsCyclophosphamide Fludarabine Interleukin-2

Overview

Phase: Phase 1
Intervention: TIL
Conditions: Solid Tumor, Adult
Sponsor: Centre Hospitalier Universitaire Vaudois
Enrollment: 6
Locations: 1
Primary Endpoint: Feasibility of TIL-ACT in combination with LDI - successful Rapid Expansion Protocol (REP): Number of patients for whom TIL cultures
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Single center, single arm phase Ib trial to test the feasibility and safety of Tumor- Infiltrating Lymphocyte-Adoptive Cell Therapy (TIL-ACT) combined with low-dose irradiation in patients with advanced or metastatic solid tumors. The trial is based on lymphodepleting chemotherapy followed by low dose irradiation (LDI), and then ACT utilizing ex vivo expanded TILs in combination with high dose IL-2 (optional, depending on patient's tolerance). LDI will be administered once to metastatic lesions using tomotherapy.

Detailed Description

The objective of the trial is to define the feasibility and safety of TIL-ACT in combination with low-dose irradiation (LDI) in patients with advanced or metastatic solid tumors. Study treatment will begin with intravenous (IV) non-myeloablative (NMA) lymphodepleting chemotherapy composed by fludarabine and cyclophosphamide. Both treatments will be started on the same day. Fludarabine will be administered for five days, and cyclophosphamide for two days. Low-dose irradiation (LDI) will be then administered once, to up to 20 measurable tumor lesions using tomotherapy. TIL infusion will be performed intravenously followed by high dose IL-2 administration every eight hours, for a maximum of eight doses. Supportive care will be given as needed during the whole treatment period. Patients achieving a stable disease, partial response or complete response after TIL-ACT treatment will then enter a follow-up period for 5 years.

Registry

clinicaltrials.gov

Start Date

September 1, 2019

End Date

March 5, 2021

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Centre Hospitalier Universitaire Vaudois

Responsible Party

Principal Investigator

George Coukos, MD, PhD

Professor

Centre Hospitalier Universitaire Vaudois

Eligibility Criteria

Inclusion Criteria

•Patients with locally advanced (not radically treatable) or metastatic solid tumors with the below cancer types, who progressed after at least one standard therapy for advanced disease, or for whom such therapy was proven to be intolerable, or is considered inappropriate. Prior immunotherapy is allowed.
•Breast cancer: irrespective of hormone receptor, Human epidermal growth factor receptor 2 (HER2) status or molecular subtype.
•Non-small cell lung cancer (NSCLC): irrespective of histological or molecular subtypes.
•Ovarian cancer: patients with high-grade serous ovarian cancer (HGSOC).
•Colon cancer: irrespective of molecular subtype.
•Other solid tumor: Patients with any other histology (any molecular subtype) with the exception of primary brain tumors, as well as cutaneous, mucosal, and ocular/uveal melanoma.
•Patients who have previously undergone tumor resection or biopsy and for whom pre-REP TILs are already available and adequate for further REP expansion. The following conditions have to be met:
•a. The Manufacturing facility / sponsor representative confirms that adequate pre-REP material (in quantity and quality) is available to move to REP.
•At least one lesion accessible to biopsy for translational research (TR) at baseline and D30, without putting the patient at unusual risk. Every effort should be made to obtain a fresh tumor biopsy upon enrolment, if previous collection of tissue is judged insufficient for study translational endpoints. The following exceptions are accepted for the baseline biopsy:
•a. Tumor material was properly collected for all protocol translational endpoints during harvesting surgery or biopsy for the TIL production (pre-REP) and no intercurrent anticancer therapy has been administered since that surgery or last biopsy. If patient has been treated with any antitumor therapy that may have altered the tumor microenvironment at the estimation of the PI, a repeat biopsy should be performed.