TIL Therapy for Metastatic Ovarian Cancer

Metastatic Ovarian Cancer Clinical Trial

Official title:

T Cell Therapy for Patients With Metastatic Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02482090
• Other study ID #: GY1508
• Status: Completed
• Phase: Phase 1
• First received: June 23, 2015
• Last updated: August 14, 2017
• Start date: July 2015
• Est. completion date: April 2017

Study information

• Verified date: August 2017
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: April 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Cyclophosphamide
Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
• Fludarabine
Fludarabine 25 mg/m2 is administered on day -5 to day -1.

Biological:
• TIL infusion
The maximum number of expanded TILs are infused over 30-45 minutes on day 0.

Drug:
• Interleukin-2
Interleukin-2 is administered as a continous i.v. infusion in a decrescendo regimen (18 MIU/m3 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU/m2 IL-2 over 24 hours followed by 4,5 MIU/m2 IL-2 over another 24 hours for three days).

Locations

Country	Name	City	State
Denmark	Center for Cancer Immune Therapy Dept. of Hematology/oncology	Copenhagen	Herlev

Sponsors (1)

Lead Sponsor	Collaborator
Inge Marie Svane

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and type of reported adverse events	Determine the safety of the administration of TIL therapy including lymphodepleting chemotherapy and Interleukin-2 for patients with metastatic Ovarian Cancer by reporting adverse events according to CTCAE v. 4.0.	0-24 weeks
Secondary	Treatment related immune responses	To evaluate the immunological impact of TIL therapy for patients with metastatic Ovarian Cancer	Up to 12 months
Secondary	Objective response rate	Clinical responses will be evaluated by RECIST 1.1.	Up to 12 months
Secondary	Overall Survival	Overall Survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.	Up to 12 months
Secondary	Progression free survival	Progression free survival (PFS), defined as the time from treatment initiation to disease progression, relapse or death due to any cause, which ever comes first, will be described with Kaplan Meier curve.	Up to 12 months