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TIL Therapy for Metastatic Ovarian Cancer

Primary Purpose

Metastatic Ovarian Cancer

Status
Completed
Phase
Phase 1
Locations
Denmark
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
TIL infusion
Interleukin-2
Sponsored by
Inge Marie Svane
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Ovarian Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

  • Center for Cancer Immune Therapy Dept. of Hematology/oncology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patient group

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
June 23, 2015
Last Updated
August 14, 2017
Sponsor
Inge Marie Svane
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1. Study Identification

Unique Protocol Identification Number
NCT02482090
Brief Title
TIL Therapy for Metastatic Ovarian Cancer
Official Title
T Cell Therapy for Patients With Metastatic Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
July 2015 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
April 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Inge Marie Svane

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Ovarian Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patient group
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cyclophospamide
Intervention Description
Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludarabinephosphate, Fludara
Intervention Description
Fludarabine 25 mg/m2 is administered on day -5 to day -1.
Intervention Type
Biological
Intervention Name(s)
TIL infusion
Other Intervention Name(s)
T Cell infusion
Intervention Description
The maximum number of expanded TILs are infused over 30-45 minutes on day 0.
Intervention Type
Drug
Intervention Name(s)
Interleukin-2
Other Intervention Name(s)
IL-2, Proleukin
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number and type of reported adverse events
Description
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.
Time Frame
0-24 weeks
Secondary Outcome Measure Information:
Title
Treatment related immune responses
Description
To evaluate the immunological impact of TIL therapy for patients with metastatic Ovarian Cancer
Time Frame
Up to 12 months
Title
Objective response rate
Description
Clinical responses will be evaluated by RECIST 1.1.
Time Frame
Up to 12 months
Title
Overall Survival
Description
Overall Survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.
Time Frame
Up to 12 months
Title
Progression free survival
Description
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.
Time Frame
Up to 12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Inge Marie Svane, Prof., MD
Organizational Affiliation
Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Magnus Pedersen, MD
Organizational Affiliation
Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Cancer Immune Therapy Dept. of Hematology/oncology
City
Copenhagen
State/Province
Herlev
ZIP/Postal Code
2730
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
30718808
Citation
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. Erratum In: Br J Cancer. 2019 Apr;120(8):870.
Results Reference
derived
PubMed Identifier
26308285
Citation
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.
Results Reference
derived

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TIL Therapy for Metastatic Ovarian Cancer

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