Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Interferons

Interferon-alpha

Interferon alpha-2

Tubulin Modulators

Antimitotic Agents

Antiviral Agents

Immunologic Factors

* Carboplatin-paclitaxel day1, q3 weeks, 6x, plus
* Tumor Infiltrating Lymphocytes (TIL) starting 14 days after the 2nd chemotherapy cycle, q3 weeks, 3x.

* 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.

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

Tumor Infiltrating Lymphocytes (TIL)

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.

Interferon Alfa 2A

Judith Kroep, MD, PhD

Els Verdegaal, PhD

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 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.

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.

Adoptive T Cell Therapy in Patients With Recurrent Ovarian Cancer

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.

Clinical response according to RECIST 1.1 criteria and immune response criteria (irRC)

Disease control rate (DCR: CR+PR+SD) at 6 months

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.

Overall Survival (OS) is defined as: the duration from the time of start of chemotherapy until death from any cause.

Leiden University Medical Center

MD PhD

Spots Global Cancer Trial Database for interferon alfa 2a