Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

for CRC patients with non-resectable hepatic metastases: surgery for CRC combined with RFA.

for CRC patients with resectable metastases: surgery only without RFA.

Robert MALAFOSSE, MD

Cindy Neuzillet, MD

The primary objective of the study aims to compare soluble CD154 (CD40L) levels before and after radiofrequency ablation (RFA) in patients with colorectal cancer (CRC) liver metastases.

The secondary objectives aims:

* to compare soluble CD154 (sCD40-L) levels before and after treatment by RFA or surgery alone in patients with CRC liver metastases;
* to study the feasibility and reliability of soluble CD154 (sCD40-L) levels to detect and quantify the induction of immun response in CRC liver metastases patients after RFA;
* to study the impact of surgery on plasma soluble CD154 levels;
* to study association between CD154 expression level before and after RFA in CRC liver metastases patients and relapses rate at 1 year.

Radiofrequency ablation (RFA) of colorectal liver metastases activates a specific T-cell response that is ineffective in avoiding recurrence. Local immunomodulation garnered interests as a way to improve the immune response. It was interesting in improving the RFA immune response priming to propose a curative treatment of colorectal cancer (CRC) based on antitumor immunity. Early study of the investigators demonstrated that the RFA did not increase the tumor infiltrating lymphocytes in secondary distant tumors of patients and in mice model and could not avoid relapse. The lack of an effective distant immune response in patients treated with RFA confirmed the relevance of the combination strategy.

Another study on the predictive value of cytokines/chemokines in rectal cancer (RC) patients receiving chemoradiation therapy (CRT) demonstrate that, the pre-CRT levels of soluble CD40-ligand (sCD40L) and the post-CRT levels of chemokine ligand-5 (CCL-5) were significantly associated with the depth of tumor invasion and with venous invasion. A significant correlation between pre-CRT platelet counts and sCD40L was observed in patients with a favorable response.

Today there is no validated biomarker for the indication of immunotherapy after local treatment on metastases of colorectal cancer.

This is a prospective, monocentric study which will be realized with the routine care and usual management. There will be any added intervention for enrolled patients during the study. All eligible patients will be enrolled and followed in the Department of digestive surgery of Ambroise Paré Hospital - APHP.

The duration of enrollment will last 6 months. The duration of follow-up for each patient will be up to 12 month.

Data collection: the medical data will be collected and recorded by Doctor Malafosse in a Excel file.

Standard plasma sampling (15 ml) as usual care, with the following timeframe:

* preoperative (baseline);
* at 24 hours post-operative;
* at 2 months post-operative.

Colorectal Cancer Immunomonitoring Combined With Radiofrequency ablatIon

Colorectal Cancer Immunomodulation Combined to Radiofrequency ablatIon

Plasma CD154 level dosage realized by ELISA in patients with CRC liver metastases.

Plasma CD154 level dosage in patients underwent surgery for CRC.

Intraclass correlation of coefficient to evaluate the feasibility and reliability of plasma CD154 level dosage in triplicate with CRC patients.

Clinical evolution parameters according to RECIST criteria.

Assistance Publique - Hôpitaux de Paris

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

16 patients recruited at the end of breast cancer treatment and followed during 9 months

Patients recruited at breast cancer before any treatment: one blood sample to provide comparative values.

16 patients will be recruited at the end of treatment: an immunoprofiling analysis will be performed out of a blood sample about 1 month, 5 months and 9 months after treatment.

8 patients will be recruited at diagnosis: a immune profile analysis will be performed before the start of treatment. This will give comparative values for the immune system cells and molecules.

Immunomonitoring

Leila Gofti-Laroche, PharmD

Leila GOFTI-LAROCHE

This study aim to determine kinetic of post treatment recovery/variation of a panel of innate and adaptative immune system cells and molecules.

The results should allow to determine the optimal post treatment immunomonitoring timing and panel to be used for future studies.

There is a complexe interaction between tumor cells ans host immunity. Immunity system (IS) is clearly involved in cancer developement control, and it is suggested that it could participate to the response to anti cancer treatment.

There is however no validated immunomonitoring strategy to allow a reliable patient's immune status along time, and particularly after treatment.There are scarce existing information on immunologic reconstitution profile recovery after treatment.

This study aim to perform immunomonitoring in young patients with cancer to describe kinetic of recovery/variation of a panel of innate and adaptative immune system cells and molecules, selected by their potential relevance according to literature.

The concerned population are young women (˂40 yo) with breast cancer.

There will be 2 patients cohorts A or "End of treatment" : patients recruited at the end of treatment (study cohort) B or "Diagnosis" : Patients recruited at diagnosis (reference values)

This study should contribute to give sufficient data to determine the pertinent timing and cells/molecules panel to evaluate immunity profiling after treatment.

These results could be used for further studies.

blood samples that will be destroyed after publications.

Feasibility Study on the Characterization of the Immune Profile of Young Patients After Treatment for Breast Cancer

Analysis of immune profile implies to evaluate changes of about 30 distinct immune cell (sub)types with their activation markers. These analyses are conducted at 3 time points for cohort "A or End of treatment" (1, 5, 9 months) and once for cohort "B or Diagnosis" before treatment start :

-% and counts of immune cell populations (B-lymphocytes, T-lymphocytes, dendritic cells)

* activation levels of cell subpopulations
* Secretion of cytokines after activation
* Determination of cytokines and chemokines after activation (picograms/ml) Description of the evolution of the parameters measured for cohort "A or End of treatment" with comparison to normal values (data from the EFS cohort and from cohort "B or Diagnosis") Analysis of the reconstitution kinetic should allow us to determine wich biological parameters (immune cell (sub)types and their activation markers) will be most relevant to study immune profile reconstitution for further studies.

number of samples analysed versus planned, quality of the results

The objective is to determine the best moment for analysis of immune system reconstitution (cf outcome 1 measures) For each patient, and each immune system marker tested (cells/molecules): kinetic analysis of return to values comparable to reference values (data from the EFS = french blood establishment and the 8 patients tested before the start of treatment).

University Hospital, Grenoble

Rare Diseases

Carcinoma

Chronic Graft Versus Host Disease

as described patietns with solid cancer about to be treated with anticancer therapies

normal populations who domated blood for further use

Hovav Nechushtan, MD PHD

Moshe sade, BSC

Tamar Hamburger, BA

hovav nechushtan, md phd

Hovav Nechushtan, MD PhD

Tumors have a systemic immune modifying effect. They affect the immune system similarly to states of chronic inflammation and these effects can:

* be monitored through analysis of nk t and myeloid cells mainly through studies of the zeta chain but also through other means
* may be decreased following effective anticancer therapy - may even be used to study the effectiveness of anticancer therapy
* are important to monitor if the investigators plan on formulation of systemic immune therapy Thus immumonitoring of systemic blood cells may turn out to be an important prognostic and predictive factor in many cancer types

CD247 Known also as the zeta chain is important for relaying T-cell induced signal transduction.

Interestingly studies by Baniash and others have demonstrated that this chain is down regulated in states of chronic inflammation and cancer in peripheral blood T cells and also in NK cells However there has not been a prospective study of this marker in cancer and control patients such a study will reveal not only the levels of CD247 in immune cells of cancer patients compared to controls but may reveal the effect of anticancer therapies on CD247 in cancer patients such a study may contribute significantly to our ability to monitor systemic immune system characteristics in cancer patients and help in any further studies of immunomodulation such as vaccination schemes in such patients

The investigators will collect peripheral blood for facts analysis of intracellular levels of proteins.

Some of these cells may be frozen for longer periods of time for comparison with other new samples.

Study of Blood Immune Cells in Cancer Patients Compared to Controls

Observational Immunomonitoring Study of NK/T and Myelocites Status in Cancer Patients and Controls

Hopefully by this time the investigators will be able to see if there are lower zeta chain intracellular expression levels in cancer patients and whether response to therapy enhances recovery of zeta chain

intracellular levels of cd247 compared to other intracellular proteins and other markers of immune response will be monitored in patients with cancer and a control group in cancer patients the investigators will conduct several tests to analyze effects of therapy

Hebrew University of Jerusalem

Hadassah Medical Organization

Hovav Nechushtan senior Lecturer MD PhD

Nervous System Diseases

Glioblastoma

Central Nervous System Neoplasms

Nervous System Neoplasms

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Vaccines

Temozolomide

Poly ICLC

Interferons

Immunologic Factors

IMA 950

Pierre-Yves Dietrich, Professor

RATIONALE : IMA 950 is multi tumour-associated peptides (TUMAPs) vaccine, these peptides have been identified on primary glioblastoma multiforme (GBM) cells. Poly-ICLC is a potent vaccine adjuvant with broad innate and adaptive immune enhancing effects. IMA 950 and Poly-ICLC will be administered to patients alongside standard primary therapy for glioblastoma. This includes the alkylating drug temozolomide (TMZ). Effective vaccine-induced immune responses associated with prolonged survival have been observed in glioblastoma patients during TMZ adjuvant therapy, suggesting a possible synergistic effect. A second component of glioblastoma standard treatment is external beam irradiation of the tumor site post-surgery. As a side effect, potentially beneficial tumor-infiltrating immune cells may also be killed by radiation. However, the combination of radiation with immunotherapy has been suggested to be favorable both in pre-clinical models.

OBJECTIVES

Primary

* Tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with temozolomide, using CTCAE V 4.0.
* Immunogenicity of IMA950 plus Poly-ICLC when given together with temozolomide.

Secondary

* 6, 9 month progression free survival (PFS) using gadolinium enhanced MRI and clinical assessment according to revised RANO criteria
* Overall survival (OS)
* Immunologic endpoints (correlation between clinical and immunological responses):
* evaluation of peptide immunogenicity by tetramer staining
* analysis of memory, activation and homing marker expression by tetramer positive cells
* analysis of cytokine secretion and proliferation by antigen-specific CD4 and CD8 T cells
* analysis of the presence of T regulatory and myeloid-derived suppressor cells
* The immunological analyses will be performed on:
* peripheral blood mononuclear cells (PBMC)
* cultures of skin punch biopsy at delayed-type hypersensitivity (DTH) site
* tumor-infiltrating lymphocytes (TIL) if brain tissue is available at recurrence

OUTLINE

This is a monocentric, open label, one cohort, safety and immunogenicity, Phase I/II study.

A maximum of 16 HLA-A2 positive patients with newly diagnosed glioblastoma will be enrolled into the study after treatment with radiation therapy and concurrent temozolomide.

All patients will receive the same dose of IMA950 with Poly-ICLC and follow the same vaccination schedule which comprises a Vaccination Induction Phase of 4 intensive vaccinations, followed by a Vaccination Maintenance Phase of five vaccinations over a longer period.

The Vaccination Induction Phase will start a minimum of 7 days after the final radiotherapy/TMZ dose of CRT and 28 days (+7 days) prior to the first scheduled dose of adjuvant TMZ.

This will ensure that all 4 vaccinations in the Induction Phase will be administered a week after immunosuppressive therapy (i.e. combined radiotherapy and temozolomide) and will finish a week prior to the start of adjuvant TMZ.

Two Phases :

Induction phase, patient receive the first 4 doses of Poly ICLC mixed with IMA 950 Peptide based vaccine (subcutaneously or IM) on days 1,8,15, and 21 in absence of unacceptable toxicity or disease progression.

Maintenance Phase, patient receive Poly ICLC mixed with IMA 950 Peptide based vaccine (SC or IM) on day 21 of each adjuvant temozolomide cycle in absence unacceptable toxicity or disease progression.

Immunomonitoring assessments will be performed at 8 time points with blood samples collection and one DTH site analysis(after vaccination 5).

Brain MRI will be performed every two months for disease assessment.

N.B. :

An amendment has been accepted by Swissmedic and Local Ethics committee on september 2014, after suboptimal immunomonitoring preliminary assessments, the schedule of administration has been changed in order to improve the immunogenicity of the vaccine, as follows :

* injection of mixed peptides and adjuvant Poly ICLC
* 4 vaccinations in the induction phase instead of 6
* one site of injection (thigh)
* two arms for the next 10 patients to be included that will be equally divided in 2 groups : one group will be vaccinated subcutaneously and the other intramuscularly.

Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma

Phase I/II Study of Intradermal IMA950 Peptide-based Vaccine Adjuvanted With Intra Muscular Poly-ICLC in Combination With Temozolomide in Newly Diagnosed HLA-A2 Glioblastoma Patients

Correlation between clinical and immunological response. Blood sampling at baseline (week 4 and 5 after beginning of radiotherapy with concomitant temozolomide) and at week 10,11,12,16,19,23,27 and 31.

Punch biopsy at DTH (Delayed Type Hypersensitivity) site performed 48h after DTH skin test 7 days after Vaccination 7.

* evaluation of peptide immunogenicity by tetramer staining
* analysis of memory, activation and homing marker expression by tetramer positive cells
* analysis of cytokine secretion and proliferation by antigen-specific CD4 and CD8 T cells
* analysis of the presence of T regulatory and myeloid-derived suppressor cells

Immatics Biotechnologies GmbH

Oncovir, Inc.

University Hospital, Geneva

Professor

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

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

Ovarian Cancer

Ovarian Epithelial Cancer

Poly(ADP-ribose) Polymerase Inhibitors

Maintenance treatment of adult patients with newly diagnosed advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (FIGO stages III and IV) with or without BRCA1/2 mutation who have had a partial or complete response to first-line platinum-based chemotherapy.

Single-agent maintenance treatment of adult patients with primary, recurrent, platinum-sensitive epithelial ovarian, fallopian tube or peritoneal cancer who have responded (completely or partially) to platinum-based chemotherapy.

Blood sampling during PARP inhibitor therapy

blood samples

This study concerns the creation of a biological collection (blood samples) in patients with Epithelial Ovarian Cancer in in order to describe the immune response with PARP inhibitors.

The aim is to assess the impact of anti-PARP on peripheral immune populations and the amount of DNA circulating; to correlate these data with tumor infiltration, with the initial clinical characteristics and with the clinical course; compare the immunogenic effect of different anti-PARPs.

5 specific blood samples :

* On the first day of anti-PARP treatment (before taking the first dose)
* Second month of anti-PARP treatment
* Fourth month of anti-PARP treatment
* Sixth month of anti-PARP treatment
* At relapse or cessation of anti-PARP treatment

For each blood sample

* 1 heparinized tube (5 mL) for plasmatheque
* 1 heparinized tube (5 mL) for immunophenotyping,
* 4 EDTA tubes (4 x 10 mL) for PBMC collection (cryopreservation).
* 1 EDTA tube (10mL) for quantification of circulating tumor DNA.

Immuno Monitoring in Patient With Epithelial Ovarian Cancer Eligible to PARP Inhibitors

Realization of a circulating tumor DNA bank

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Colorectal Cancer Immunomonitoring Combined With Radiofrequency ablatIon	NCT04420013	Colorectal Canc... Radiofrequency ...		18 Years -	Assistance Publique - Hôpitaux de Paris
Feasibility Study on the Characterization of the Immune Profile of Young Patients After Treatment for Breast Cancer	NCT04645849	Breast Cancer	Immunomonitorin...	18 Years - 39 Years	University Hospital, Grenoble
Study of Blood Immune Cells in Cancer Patients Compared to Controls	NCT01312701	Solid Carcinoma		16 Years -	Hadassah Medical Organization
Feasibility Study on the Characterization of the Immune Profile of Young Patients After Treatment for Breast Cancer	NCT04645849	Breast Cancer	Immunomonitorin...	18 Years - 39 Years	University Hospital, Grenoble
Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma	NCT01920191	CNS Tumor, Adul...	IMA 950 Poly ICLC Immunomonitorin...	18 Years -	University Hospital, Geneva
Immuno Monitoring in Patient With Epithelial Ovarian Cancer Eligible to PARP Inhibitors	NCT04675320	Ovarian Cancer	blood samples	18 Years -	Centre Georges Francois Leclerc
Colorectal Cancer Immunomonitoring Combined With Radiofrequency ablatIon	NCT04420013	Colorectal Canc... Radiofrequency ...		18 Years -	Assistance Publique - Hôpitaux de Paris
Study of Blood Immune Cells in Cancer Patients Compared to Controls	NCT01312701	Solid Carcinoma		16 Years -	Hadassah Medical Organization

Spots Global Cancer Trial Database for immunomonitoring