Clinical trial NCT02482090: TIL Therapy for Metastatic Ovarian Cancer
Official title: T Cell Therapy for Patients With Metastatic Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Ovarian Cancer
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
First posted: 2015-06-25
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell acitivation and proliferation in vivo.

Recent studies suggest, that TIL therapy works in other cancers than Metastatic Melanoma, including Ovarian Cancer. In this study TIL therapy is administered to patients with metastatic Ovarian Cancer.

Detailed description: Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell acitivation and proliferation in vivo.

Objectives:

To evaluate safety and feasibility when treating patients with metastatic ovarian cancer with ACT with TILs.

To evaluate treatment related immune responses To evaluate clinical efficacy

Design:

Patients will be screened with a physical exam, medical history, blood samples and ECG.

Patients will undergo surgery to harvest tumor material for TIL production. Patients is admitted day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7.

On day 0 patients receive TIL infusion and shortly after starts IL-2 infusion continually following the decrescendo regimen.

The patients will followed until progression or up to 5 years

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed high grade serous adenokarcinoma ovarian cancer metastasis available for surgical resection (more than 1 cm3) and residual measurable disease after resection
* Progression/reccurence of ovarian cancer after 1. line platin based chemotherapy or progression/reccurence after 2. line or additional chemotherapy
* ECOG performance status 0-1
* Life expectancy \> 6 months
* No significant toxicity from prior treatments, except sensoric- and motoric neuropathia and/or alopecia
* Adequate renal, hepatic and hematological function
* Women of childbearing potentil (WOCBP) must be using an effective method of contraception during treatment and for at least 6 months after completion of treatment
* Able to comprehend the information given and willing to sign informed consent

Exclusion Criteria:

* Other malignancies, unless followed for ≥ 5 years with no sign of disease
* Severe allergies, history of anaphylaxis or known allergies to the administered drugs.
* Serious medical or psychiatric comorbidity
* Creatinine clearance \< 70 ml/min
* Acute or chronic infection with e.g. HIV, hepatitis, tuberculosis
* Severe and active autoimmune disease
* Pregnant and nursing women
* Need for immunosuppressive treatment, e.g. corticosteroids or methotrexate
* Concomitant treatment with other experimental drugs
* Patients with uncontrolled hypercalcemia
* Less than four weeks since prior systemic antineoplastic treatment at the time of treatment

Primary outcomes:
measure: Number and type of reported adverse events
timeFrame: 0-24 weeks
Secondary outcomes:
measure: Treatment related immune responses
timeFrame: Up to 12 months
measure: Objective response rate
timeFrame: Up to 12 months
measure: Overall Survival
timeFrame: Up to 12 months
measure: Progression free survival
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Center for Cancer Immune Therapy Dept. of Hematology/oncology
state: Herlev
Study officials:
affiliation: Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
name: Inge Marie Svane, Prof., MD
role: STUDY_DIRECTOR
affiliation: Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
name: Magnus Pedersen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Westergaard MCW, Andersen R, Chong C, Kjeldsen JW, Pedersen M, Friese C, Hasselager T, Lajer H, Coukos G, Bassani-Sternberg M, Donia M, Svane IM. Tumour-reactive T cell subsets in the microenvironment of ovarian cancer. Br J Cancer. 2019 Feb;120(4):424-434. doi: 10.1038/s41416-019-0384-y. Epub 2019 Feb 5.
citation: Andersen R, Donia M, Westergaard MC, Pedersen M, Hansen M, Svane IM. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma. Hum Vaccin Immunother. 2015;11(12):2790-5. doi: 10.1080/21645515.2015.1075106.