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TIL Therapy for Metastatic Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT02482090
Recruitment Status : Completed
First Posted : June 25, 2015
Last Update Posted : August 16, 2017
Sponsor:
Information provided by (Responsible Party):
Inge Marie Svane, Herlev Hospital

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.


Condition or disease Intervention/treatment Phase
Metastatic Ovarian Cancer Drug: Cyclophosphamide Drug: Fludarabine Biological: TIL infusion Drug: Interleukin-2 Phase 1

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  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: T Cell Therapy for Patients With Metastatic Ovarian Cancer
Study Start Date : July 2015
Actual Primary Completion Date : December 2016
Actual Study Completion Date : April 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

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 Name: Cyclophospamide

Drug: Fludarabine
Fludarabine 25 mg/m2 is administered on day -5 to day -1.
Other Names:
  • Fludarabinephosphate
  • Fludara

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

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:
  • IL-2
  • Proleukin




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Treatment related immune responses [ Time Frame: Up to 12 months ]
    To evaluate the immunological impact of TIL therapy for patients with metastatic Ovarian Cancer

  2. Objective response rate [ Time Frame: Up to 12 months ]
    Clinical responses will be evaluated by RECIST 1.1.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02482090


Locations
Denmark
Center for Cancer Immune Therapy Dept. of Hematology/oncology
Copenhagen, Herlev, Denmark, 2730
Sponsors and Collaborators
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 automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Inge Marie Svane, M.D., Professor, Herlev Hospital
ClinicalTrials.gov Identifier: NCT02482090     History of Changes
Other Study ID Numbers: GY1508
First Posted: June 25, 2015    Key Record Dates
Last Update Posted: August 16, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents