TIL Therapy for Metastatic Ovarian Cancer

Inge Marie Svane

Status and phase: Completed; Phase 1

Conditions: Metastatic Ovarian Cancer

Treatments: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: TIL infusion; Drug: Interleukin-2

Study type: Interventional

Funder types: Other

Identifiers

NCT02482090

GY1508

Details and patient eligibility

About

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.

Full 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

Enrollment: 6 patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Patient group

Experimental group

Description:

All patients receive the same treatment. Alle patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once. Stem Cells are harvested a minimum of 3 weeks before treatment for potential later use if the patients are having difficulties recovering from the lymphodepleting chemotherapy. The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered in an i.v. continous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days. Stem Cells can be administered after treatment if needed.

Treatment:

Drug: Interleukin-2

Biological: TIL infusion

Drug: Cyclophosphamide

Drug: Fludarabine