TIL Therapy for Metastatic Ovarian Cancer

NCT ID: NCT02482090

Last Updated: 2017-08-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-31

Study Completion Date

2017-04-30

Brief Summary

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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

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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

Conditions

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Metastatic Ovarian Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.

Fludarabine

Intervention Type DRUG

Fludarabine 25 mg/m2 is administered on day -5 to day -1.

TIL infusion

Intervention Type BIOLOGICAL

The maximum number of expanded TILs are infused over 30-45 minutes on day 0.

Interleukin-2

Intervention Type DRUG

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).

Interventions

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Cyclophosphamide

Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.

Intervention Type DRUG

Fludarabine

Fludarabine 25 mg/m2 is administered on day -5 to day -1.

Intervention Type DRUG

TIL infusion

The maximum number of expanded TILs are infused over 30-45 minutes on day 0.

Intervention Type BIOLOGICAL

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).

Intervention Type DRUG

Other Intervention Names

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Cyclophospamide Fludarabinephosphate Fludara T Cell infusion IL-2 Proleukin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Inge Marie Svane

OTHER

Sponsor Role lead

Responsible Party

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Inge Marie Svane

M.D., Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Inge Marie Svane, Prof., MD

Role: STUDY_DIRECTOR

Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730

Magnus Pedersen, MD

Role: PRINCIPAL_INVESTIGATOR

Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730

Locations

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Center for Cancer Immune Therapy Dept. of Hematology/oncology

Copenhagen, Herlev, Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type DERIVED
PMID: 30718808 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26308285 (View on PubMed)

Other Identifiers

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GY1508

Identifier Type: -

Identifier Source: org_study_id

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