TIL Therapy in Combination With Checkpoint Inhibitors for Metastatic Ovarian Cancer

NCT03287674 | Completed Phase 1 Results DMC

• 1 other identifier: GY1721
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. 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 activation and proliferation in vivo. The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect.

Conditions

Metastatic Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Reported Adverse Events by Type

  Determine the safety of TIL therapy in combination with checkpoint inhibitors for patients with ovarian-, fallopian tube or primary peritoneal cancer by reporting adverse events according to CTCAE v. 4.0.

  Up to 12 months

Secondary Outcomes (4)

• Treatment Related Immune Responses

  Until protocol end, until 6 months after TIL infusion

• Objective Response Rate

  Assessed up to 12 months after therapy.

• Overall Survival

  Up to 3 years after TIL infusion

• Progression Free Survival

  Up to 12 months after TIL infusion

Study Arms (1)

Patient group

EXPERIMENTAL

All patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks. The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses. The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13. Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: TIL infusion; Drug: Interleukin-2; Drug: Ipilimumab; Drug: Nivolumab

Interventions

Cyclophosphamide DRUG

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

Patient group

Fludarabine DRUG

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

Also known as: Fludarabine phosphate

Patient group

TIL infusion BIOLOGICAL

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

Also known as: TILs

Patient group

Interleukin-2 DRUG

Interleukin-2 is administered as a daily low-dose subcutaneous injection of 2 MIU for a total of 14 days.

Also known as: IL-2

Patient group

Ipilimumab DRUG

One dose of Ipilimumab 3 mg/kg is administered 14 days prior to surgical removal of tumor tissue for TIL expansion.

Patient group

Nivolumab DRUG

Nivolumab 3 mg/kg is administered on day -2 before TIL infusion and every 2 weeks for a total of 4 doses.

Patient group

Eligibility Criteria

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

You may qualify if:

• Histological proven advanced ovarian-, fallopian tube or primary peritoneal cancer with the possibility of surgical removal of tumor tissue of \> 1 cm3.
• Progressive or recurrent resistant disease after platin-based chemotherapy (platinum resistant) or progressive or recurrent disease after second line or additional chemotherapy.
• Age: 18 - 70 years.
• ECOG performance status of ≤1 (Appendix 2).
• Life expectancy of \> 6 months.
• At least one measurable parameter in accordance with RECIST 1.1 -criteria's.
• No significant toxicities or side effects from previous treatments, except sensoric- and motoric neuropathy and/or alopecia
• Sufficient renal, hepatic and hematological function
• 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
• Known hypersensitivity to one of the active drugs or one or more of the excipients.
• Severe medical or psychiatric conditions
• Creatinine clearance \< 70 ml/min. In selected cases it can be decided to include a patient with a GFR \< 70 ml/min with the use of a reduced dose of chemotherapy.
• Acute/chronic infection with HIV, hepatitis, syphilis among others.
• Severe allergies or previous anaphylactic reactions.
• Active autoimmune disease
• Pregnant women and women breastfeeding.
• Need for immunosuppressive treatment e.g. corticosteroids or methotrexate. In selected cases a systemic dose of ≤10 mg prednisolone or a transient planned treatment that can be stopped before TIL therapy can be tolerated.
• Simultaneous treatment with other experimental drugs.
• Simultaneous treatment with other systemic anti-cancer treatments.
• Patients with active and uncontrollable hypercalcaemia.

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (1)

Center for Cancer Immune Therapy Dept. of Hematology/oncology

Copenhagen, 2730, Denmark

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2; Ipilimumab; Nivolumab

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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Anders Kverneland, MD
• Organization: National Center for Cancer Immune Therapy, Herlev Hospital

anders.kverneland@regionh.dk

38686467

Study Officials

• Inge Marie Svane, Prof., M.D.

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

  STUDY DIRECTOR

• Magnus Pedersen, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: September 14, 2017
• First Posted: September 19, 2017
• Study Start: October 9, 2017
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: March 1, 2023
• Results First Posted: March 22, 2021

Record last verified: 2023-02

Locations

DK (1)