TIL Therapy for Metastatic Ovarian Cancer

August 14, 2017 updated by: Inge Marie Svane

T Cell Therapy for Patients With Metastatic Ovarian Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Herlev
      • Copenhagen, Herlev, Denmark, 2730
        • Center for Cancer Immune Therapy Dept. of Hematology/oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patient group

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.
Drug: Cyclophosphamide
Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
Other Names:
  • Cyclophospamide
Biological: TIL infusion
The maximum number of expanded TILs are infused over 30-45 minutes on day 0.
Other Names:
  • T Cell infusion
Drug: Fludarabine
Fludarabine 25 mg/m2 is administered on day -5 to day -1.
Other Names:
  • Fludara
  • Fludarabinephosphate
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).
Other Names:
  • Proleukin
  • IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and type of reported adverse events
Time Frame: 0-24 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: Up to 12 months
Clinical responses will be evaluated by RECIST 1.1.
Up to 12 months
Overall Survival
Time Frame: Up to 12 months
Overall Survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.
Up to 12 months
Progression free survival
Time Frame: Up to 12 months
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
Treatment related immune responses
Time Frame: Up to 12 months
To evaluate the immunological impact of TIL therapy for patients with metastatic Ovarian Cancer
Up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inge Marie Svane

Investigators

  • Study Director: Inge Marie Svane, Prof., MD, Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
  • Principal Investigator: Magnus Pedersen, MD, Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

April 1, 2017

Study Registration Dates

First Submitted

June 23, 2015

First Submitted That Met QC Criteria

June 23, 2015

First Posted (Estimate)

June 25, 2015

Study Record Updates

Last Update Posted (Actual)

August 16, 2017

Last Update Submitted That Met QC Criteria

August 14, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GY1508

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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