Adoptive T Cell Therapy in Patients With Recurrent Ovarian Cancer

NCT04072263 | Unknown Phase 1 DMC

• 1 other identifier: OVACURE
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Ovarian Cancer Recurrent

Outcome Measures

Primary Outcomes (1)

• NCI CTC criteria

  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 Outcomes (4)

• Clinical Response

  3 years

• Disease Control rate

  3 years

• Progression free survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

Study Arms (2)

Cohort 1

EXPERIMENTAL

* 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); Drug: Carboplatin; Drug: Paclitaxel

Cohort 2

EXPERIMENTAL

* 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); Drug: Interferon Alfa 2A; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Tumor Infiltrating Lymphocytes (TIL) BIOLOGICAL

Adoptive cell therapy using Tumor-Infiltrating Lymphocytes (TIL) i.v.

Cohort 1; Cohort 2

Interferon Alfa 2A DRUG

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.

Also known as: IFNalpha

Cohort 2

Carboplatin DRUG

chemotherapy i.v.

Also known as: carboplatine

Cohort 1; Cohort 2

Paclitaxel DRUG

Chemotherapy i.v.

Also known as: Taxol

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333ZA, Netherlands

RECRUITING

MeSH Terms

Interventions

Interferon alpha-2; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Judith Kroep, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Judith Kroep, MD, PhD

CONTACT

0031715263464; j.r.kroep@lumc.nl

Els Verdegaal, PhD

CONTACT

0031715263464; E.M.E.Verdegaal@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

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

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: August 28, 2019
• Study Start: August 1, 2018
• Primary Completion: August 1, 2021
• Study Completion: December 1, 2021
• Last Updated: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)