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Trial record 57 of 601 for:    Recruiting, Not yet recruiting, Available Studies | Ovarian cancer

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

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ClinicalTrials.gov Identifier: NCT04072263
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
J.R. Kroep, Leiden University Medical Center

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. We propose to 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, we will perform exploratory studies 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).


Condition or disease Intervention/treatment Phase
Ovarian Cancer Recurrent Biological: Tumor Infiltrating Lymphocytes (TIL) Drug: Interferon Alfa 2A Drug: Carboplatin Drug: Paclitaxel Phase 1 Phase 2

Detailed Description:

We propose to 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, we will perform exploratory studies 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adoptive T Cell Therapy in Patients With Recurrent Ovarian Cancer
Actual Study Start Date : August 1, 2018
Estimated Primary Completion Date : August 1, 2021
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

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 Name: carboplatine

Drug: Paclitaxel
Chemotherapy i.v.
Other Name: 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: 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 Name: IFNalpha

Drug: Carboplatin
chemotherapy i.v.
Other Name: carboplatine

Drug: Paclitaxel
Chemotherapy i.v.
Other Name: Taxol




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Clinical Response [ Time Frame: 3 years ]
    Clinical response according to RECIST 1.1 criteria and immune response criteria (irRC)

  2. Disease Control rate [ Time Frame: 3 years ]
    Disease control rate (DCR: CR+PR+SD) at 6 months

  3. 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.

  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04072263


Contacts
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Contact: Judith Kroep, MD, PhD 0031715263464 j.r.kroep@lumc.nl
Contact: Els Verdegaal, PhD 0031715263464 E.M.E.Verdegaal@lumc.nl

Locations
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Netherlands
Leiden University Medical Center Recruiting
Leiden, ZH, Netherlands, 2333ZA
Sponsors and Collaborators
Leiden University Medical Center
Investigators
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Principal Investigator: Judith Kroep, MD, PhD Leiden University Medical Center

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Responsible Party: J.R. Kroep, MD PhD, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT04072263     History of Changes
Other Study ID Numbers: OVACURE
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Interferons
Interferon-alpha
Interferon alpha-2
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors