TIL Therapy for Metastatic Ovarian Cancer

NCT02482090 | Completed Phase 1 DMC

• 1 other identifier: GY1508
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Treatment related immune responses

  Up to 12 months

• Objective response rate

  Up to 12 months

• Overall Survival

  Up to 12 months

• Progression free survival

  Up to 12 months

Study Arms (1)

Patient group

EXPERIMENTAL

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; Drug: Fludarabine; Biological: TIL infusion; Drug: Interleukin-2

Interventions

Cyclophosphamide DRUG

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

Also known as: Cyclophospamide

Patient group

Fludarabine DRUG

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

Also known as: Fludarabinephosphate, Fludara

Patient group

TIL infusion BIOLOGICAL

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

Also known as: T Cell infusion

Patient group

Interleukin-2 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).

Also known as: IL-2, Proleukin

Patient group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (1)

Center for Cancer Immune Therapy Dept. of Hematology/oncology

Copenhagen, Herlev, 2730, Denmark

Location

Related Publications (2)

• 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.

  PMID: 30718808 DERIVED

• 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.

  PMID: 26308285 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Inge Marie Svane, Prof., MD

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

  STUDY DIRECTOR

• Magnus Pedersen, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D., Professor

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: June 25, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: April 1, 2017
• Last Updated: August 16, 2017

Record last verified: 2017-08

Locations

DK (1)