Adoptive T Cell Therapy in Patients With Recurrent Ovarian Cancer (OVACURE)

March 30, 2021 updated by: J.R. Kroep, Leiden University Medical Center

The clinical benefit of standard treatment for patients with epithelial ovarian cancer (EOC) are poor. Ovarian cancer is a highly immunogenic tumor and good survival is tightly linked to the presence of tumor-infiltrating CD8+ T cells and the absence of immunosuppressive immune cells. This clear correlation between T cell infiltration and disease progression suggests that EOC may be sensitive to adoptive cell therapy by infusion of ex-vivo expanded autologous Tumor Infiltrating Lymphocytes (TIL) provided that immune suppression is reduced. Carboplatin+paclitaxel chemotherapy is directly killing tumor cells but was also shown to alleviate immunosuppression for 2 weeks coinciding with enhanced T-cell immunity, potentially creating a window of opportunity for T-cell based immunotherapy.

In addition, there is evidence that interferon alpha (IFNα) not only may work as a low toxic preconditioning regimens that creates the space required for the infused TIL but that it also supports the TIL by sustaining their persistence and indirectly their function, by upregulation of HLA class I on tumor cells and decreasing the numbers of regulatory T cells. Based on this we hypothesize that a synergistic clinical effect may be obtained when adoptive cell therapy with autologous TIL is administered during treatment with chemotherapy and IFNα. The feasibility and safety of TIL administration is studied in the window of opportunity created by carboplatin-paclitaxel chemotherapy with or without interferon alpha (IFNα). Furthermore, exploratory studies will be performed to analyze and confirm the proposed underlying mechanisms.

Tumor material for TIL production will be collected during first line debulking surgery in case of FIGO stage IIIC/IV disease (pre-OVACURE) or in case of recurrent platinum sensitive disease an extra biopsy can be planned (OVACURE).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study the feasibility and safety of TIL administration in the window of opportunity created by carboplatin-paclitaxel chemotherapy with or without interferon alpha (IFNα). Furthermore, exploratory studies will be performed to analyze and confirm the proposed underlying mechanisms.

Intervention:

Cohort 1

  • Carboplatin-paclitaxel day1, q3 weeks, 6x, plus
  • TIL starting 14 days after the 2nd chemotherapy cycle, q3 weeks, 3x.

Cohort 2

  • Carboplatin-paclitaxel day1, q3 weeks, 6x, plus
  • TIL starting 14 days after the 2nd chemotherapy cycle, q3 weeks, 3x, plus
  • IFNα (3x10e6 U daily) starting one week before the first TIL infusion for 12 weeks in total.

Study Type

Interventional

Enrollment (Anticipated)

12

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • ZH
      • Leiden, ZH, Netherlands, 2333ZA
        • Recruiting
        • Leiden University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Age ≥ 18 years.
  • Histologically proven epithelial ovarian cancer (EOC).
  • Recurrent ovarian cancer amenable to carboplatin and paclitaxel chemotherapy. Patient with primary stage III or IV EOC can participate in the pre-OVACURE to collect rest tumor during debulking surgery for TILs preservation, so TILs will be available in case of recurrent disease will develop in the future.
  • Presence of measurable progressive disease according to RECIST version 1.1 or elevated CA125 ≥ 2 times the upper normal limit (UNL) within 3 months and confirmed.
  • Expected survival of at least 3 months.
  • WHO performance status 0-2.
  • Within the last 2 weeks prior to study day 0, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified:

Lab Parameter Range Hemoglobin ≥ 6,0 mmol/l Granulocytes ≥ 1,500/µl Lymphocytes ≥ 700/µl Platelets ≥ 100,000/µl Creatinine clearance ≥ 50 min/ml Serum bilirubin ≤ 40 mol/l ASAT and ALAT ≤ 5 times the normal upper limit LDH ≤ 2 times the normal upper limit

  • Viral tests:

    • Negative for HIV type 1/2, HTLV and TPHA
    • No HBV (hepatitis B virus) antigen or antibodies against HBc in the serum
    • No antibodies against HCV (hepatitis C virus) in the serum
  • Able and willing to give valid written informed consent.
  • Prior treatment, including immunotherapy e.g. with anti-PD(L)1, is allowed but systemic therapy and radiotherapy must have been discontinued for at least two weeks before study entry.
  • Patients should have disease progression.

Exclusion Criteria:

  • Patients with brain metastases.
  • Clinically significant heart disease (NYHA Class III or IV).
  • Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders, or other conditions requiring concurrent medications not allowed during this study.
  • Active immunodeficiency disease or autoimmune disease requiring immune suppressive drugs. Vitiligo is not an exclusion criterion.
  • Other malignancy within 2 years prior to entry into the study, except for treated non-melanoma skin cancer and in situ cervical or vulva carcinoma.
  • Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  • Lack of availability for follow-up assessments.
  • Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
  • Carboplatin-paclitaxel day1, q3 weeks, 6x, plus
  • Tumor Infiltrating Lymphocytes (TIL) starting 14 days after the 2nd chemotherapy cycle, q3 weeks, 3x.
Biological: Tumor Infiltrating Lymphocytes (TIL)
Adoptive cell therapy using Tumor-Infiltrating Lymphocytes (TIL) i.v.
Drug: Carboplatin
chemotherapy i.v.
Other Names:
  • carboplatine
Drug: Paclitaxel
Chemotherapy i.v.
Other Names:
  • Taxol
Experimental: Cohort 2
  • Carboplatin-paclitaxel day1, q3 weeks, 6x, plus
  • Tumor Infiltrating Lymphocytes (TIL) starting 14 days after the 2nd chemotherapy cycle, q3 weeks, 3x, plus
  • Interferon Alpha 2A (3x10e6 U daily) starting one week before the first TIL infusion for 12 weeks in total.
Biological: Tumor Infiltrating Lymphocytes (TIL)
Adoptive cell therapy using Tumor-Infiltrating Lymphocytes (TIL) i.v.
Drug: Carboplatin
chemotherapy i.v.
Other Names:
  • carboplatine
Drug: Paclitaxel
Chemotherapy i.v.
Other Names:
  • Taxol
Drug: Interferon Alfa 2A
Interferon alpha (IFNα) s.c., may work as a low toxic preconditioning regimens that creates the space required for the infused TIL but that it also supports the TIL by sustaining their persistence and indirectly their function, by upregulation of HLA class I on tumor cells and decreasing the numbers of regulatory T cells.
Other Names:
  • IFNalpha

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NCI CTC criteria
Time Frame: 3 years
If a DLT occurs in more than one out of the three patients, the study will be stopped. If < 1 out of 3 patients have a DLT, then three additional patients will be treated. Therefore, a minimum of 3 and a maximum of 6 patients will be treated in both cohorts.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response
Time Frame: 3 years
Clinical response according to RECIST 1.1 criteria and immune response criteria (irRC)
3 years
Disease Control rate
Time Frame: 3 years
Disease control rate (DCR: CR+PR+SD) at 6 months
3 years
Progression free survival (PFS)
Time Frame: 3 years
Progression free survival (PFS) is defined as: the duration from the time of start chemotherapy until first observation of radiologically confirmed progressive disease or death due to any cause, whichever occurred first.
3 years
Overall Survival (OS)
Time Frame: 3 years
Overall Survival (OS) is defined as: the duration from the time of start of chemotherapy until death from any cause.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University Medical Center

Investigators

  • Principal Investigator: Judith Kroep, MD, PhD, Leiden University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2018

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

August 27, 2019

First Submitted That Met QC Criteria

August 27, 2019

First Posted (Actual)

August 28, 2019

Study Record Updates

Last Update Posted (Actual)

April 1, 2021

Last Update Submitted That Met QC Criteria

March 30, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OVACURE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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