Clinical trial NCT03904537: A Study of Combination of Anti-PD1 Antibody-activated TILs and Chemotherapy in Colorectal Cancer
Official title: A Phase I/II Study of Combination of Anti-Programmed Cell Death Protein 1(Anti-PD1) Antibody-activated Autologous Tumor Infiltrating Lymphocytes (TILs) and Chemotherapy in the Treatment of Stage III Colorectal Cancer.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer Stage III
Keywords: Colorectal Cancer
TIL
immunotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-04-05
Enrollment: 20
Sex: ALL
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: This study was a phase I/II trial initiated by the investigator to evaluate the safety and tolerability of anti-programmed cell death protein 1 (anti-PD1) antibody-activated autologous tumor-infiltrating lymphocytes (TILs) combined with adjuvant chemotherapy in participants with stage III colon cancer. Twenty participants were enrolled and anti-PD1 antibody-activated TILs was infused into participants after the final of adjuvant chemotherapy to assess the safety and 3-year disease-free survival.

Detailed description: Postoperative colon cancer participants received 4 to 8 cycles of XELOX regimen adjuvant chemotherapy and received anti-PD1 antibody-activated TILs on the day 15 of the final cycle of chemotherapy.

Fresh tumor tissues or sentinel lymph nodes were collected from participants with postoperative colon cancer, and the tumor tissues were digested with type IV collagenase at 37 °C for 2 to 4 hours. The cell pellet was washed, suspended in medium containing 10% AB serum, planted in a 24-well cell culture plate, and periodically changed according to the growth of the cells. After culturing for 2 to 3 weeks, TILs were co-stimulated with radioactively irradiated allogeneic peripheral blood mononuclear cells (PBMCs) and were expanded in 100 ml of Interleukin-2 (IL-2) medium in a cell culture flask. After rapid expansion for 15 days, the number of cells reached 0.1-1\*10\^10 cells. Before cell transfer, TILs were incubated with anti-PD-1 antibody, and a fraction of the TILs were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Then, autologous TILs (0.1-1\*10\^10 cells) were transferred to participants via intravenous infusion.

Eligibility criteria: Inclusion Criteria:

* Participants with stage III colorectal cancer and scheduled to receive adjuvant chemotherapy postoperation.
* Age 18 to 75 years.
* Willing to sign a durable power of attorney.
* Able to understand and sign the Informed Consent Document.
* Life expectancy of greater than six months.
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
* Adequate organ function.
* Serology:

Seronegative for HIV antibody. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

•Hematology: white blood cell count (\> 3500/mm(3)). Platelet count greater than 100,000/mm(3). Hemoglobin greater than 9.0 g/dl.

•Chemistry: Serum Alanine aminotransferase/Aspartate aminotransferase less or equal to 2.5 times the upper limit of normal.

Serum creatinine less than or equal to 1.6 mg/dl. Total bilirubin less than or equal to 1.5 mg/dl.

Exclusion Criteria:

* Previous treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) , anti-PD-1, and anti-Programmed death-ligand 1(PD-L1).
* Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
* Allogeneic tissue/organ transplantation.
* Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
* History of autoimmune disease
* Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
* Concurrent antineoplastic therapies and systemic steroid therapy.

Primary outcomes:
measure: Disease-free survival (DFS）
timeFrame: 6 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 6 months
measure: Severity of adverse events
timeFrame: 3 weeks
measure: Immune cell subgroup and cytokine level
timeFrame: 1 months
measure: The quality of life by EQ-5D-5L (EuroQol Group, Chinese versions )
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University, Cancer Center
state: Guangdong
Study officials:
References: