Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Multiple Primary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Surgery after induction therapy with IO/IO or a TKI/IO-combination, followed by maintenance therapy with nivolumab or a TKI/IO-combination.

Induction therapy wih IO/IO or a TKI/IO-combination, followed by maintenance therapy with nivolumab or a TKI/IO-combination.

Partial or complete nephrectomy by open, laparoscopic, or robotic approach.

Cytoreductive nephrectomy

Tumor biopsies, blood, and stool specimens for translational biomarker research will be sampled at baseline and after 3 or 6 months.

Tissue sampling

Niels Fristrup, MD PhD

Anne Kirstine Moeller, MD, PhD

Niels Viggo Jensen, MD

BACKGROUND: For synchronous metastatic renal cell carcinoma (RCC), surgical resection of the primary tumor in the presence of distant metastases has been the standard of therapy for select patients followed by systemic therapy. In the era of TKIs two randomized trials, CARMENA and SURTIME, have questioned the role and timing of surgery in these patients, results point towards no surgery or a deferred approach.

RATIONALE: The antitumor activity of immune checkpoint blockage (ICB) is more potent than other therapy in mRCC. The deferred cytoreductive nephrectomy approach ensures systemic therapy for all patients, avoid systemic treatment delay, and spare surgery in patients with progressive tumors. Current data only point towards a survival benefit for cytoreductive nephrectomy in intermediate risk patients, but not in poor risk patients

HYPOTHESIS: Deferred cytoreductive nephrectomy after initial nivolumab combined with ipilimumab or a TKI/IO-combination will improve OS in patients with synchronous metastatic RCC and ≤3 IMDC risk features

This is an open, randomized, multicenter comparison trial, designed to evaluate the effect of deferred cytoreductive nephrectomy compared with no surgery following initial nivolumab combined with ipilimumab or a TKI-combination, in mRCC patients with IMDC intermediate and poor risk.

OUTLINE: This is a multicenter trial, patients are stratified according to institution, treatment choice, number of IMDC risk factors, and combined elevated neutrophil-lymphocyte ratio and hyponatremia.

All patients will receive induction checkpoint immunotherapy immediately after inclusion. After 3 months or a total of 4 series of nivolumab combined with ipilimumab or a TKI/IO-combination, the patient will be discussed for resectability at the multidisciplinary meeting (MDT). Whether the patient is eligible for cytoreductive nephrectomy is at the discretion of the urologist at the local MDT. Patients with ≤ 3 IMDC risk factors and deemed suitable for cytoreductive nephrectomy will then undergo randomization. Patients deemed not suitable for surgery or have \> 3 IMDC risk features at the 3 month evaluation continue systemic therapy for 3 months, followed by a 2nd evaluation. Patients with ≤ 3 IMDC risk factors and deemed suitable for cytoreductive nephrectomy at 2nd evaluation will then undergo randomization. Patients deemed not suitable for surgery or have \> 3 IMDC risk features at the 6 month evaluation continue systemic therapy. Nivolumab may continue until unacceptable toxicity or total treatment length of 2 years from inclusion.

ARM A: Deferred cytoreductive nephrectomy, followed by maintenance nivolumab or a TKI/IO-combination.

ARM B: No surgery, receive maintenance nivolumab or a TKI/IO-combination.

Patients undergo tumor tissue, blood, and stool collection at baseline, 3 and 6 months, for planned translational research.

Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma: The NORDIC-SUN-Trial

Multicenter Randomized Trial of Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma Receiving Checkpoint Inhibitors: a DaRenCa and NoRenCa Trial Evaluating the Impact of Surgery or No Surgery. The NORDIC-SUN-Trial

Calculated from the date of inclusion, to the date of death of any cause or censored at the date at last follow-up.

Calculated from date of inclusion to date of initiation of subsequent therapy or death of any cause or censored at the date of last follow-up

Aarhus University Hospital

Niels Fristrup

MD PhD

Digestive System Diseases

Adenoma

Duodenal Diseases

Intestinal Diseases

Gastrointestinal Diseases

Patients who consent to participate in this study will have a small sample of their adenoma and normal tissue sent for molecular testing.

A small sample of the duodenal adenoma will be obtained for molecular testing. The remaining adenoma will be sent for regular histological testing.

Tissue Sampling

Michael Bourke, MBBS, FRACP

The purpose is to investigate whether polyps that look different at endoscopy, have formed via different mutations and have different risks of turning into cancer.

Laterally spreading tumours (LSTs), are polyps that have a lateral extension along the duodenal wall with minimal vertical growth. It has become evident over the last few years that rather than being a single entity requiring an accumulation of mutations, Duodenal and ampullary cancer is in fact a heterogenous disease forming via multiple distinct genetic pathways. It is therefore hypothesised that different polyp types have different genetic abnormalities, and potentially form via distinct genetic pathways, although this theory has not been widely examined.

This knowledge would be important in furthering our understanding of the development of cancer. There is accumulating evidence that genetic abnormalities may be a better predictor of cancer behaviour than histological grade. Additionally, guidelines for endoscopy surveillance are currently a one size fits all approach that do not reflect the genetic heterogeneity of the disease and the knowledge that only 5% of polyps progress to cancer. Genetic studies may assess future cancer risk to a person in polyps once removed and plan surveillance endoscopy frequency.

Adenoma tissue sample and control "regular" tissue sample

Endoscopic Characteristics of Duodenal and Ampullary Lesions

A Correlation of the Endoscopic Characteristics of Duodenal and Ampullary Laterally Spreading Tumours With Their Somatic or Germline Mutations.

The aim of this project is to look for statistically significant differences in molecular abnormalities from the three known genetic pathways, between the two different morphological types, granular and non-granular, to potentially demonstrate that these different polyps form via different genetic pathways.

Professor Michael Bourke

Director of Gastrointestinal Endoscopy

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Women at high risk for developing breast cancer

Carol J Fabian, MD

A study to examine the correlations between methylation of various genes associated with breast cancer and proliferation and cytomorphology in breast epithelial cells acquired by random periareolar fine needle aspiration of women at high risk for development of breast cancer.

A study to examine the correlation between gene promotor methylation and benign breast tissue proliferation and cytomorphology collected via random periareolar fine needle aspiration in postmenopausal women at increased risk for breast cancer.

Protocol to Examine Methylation of Tumor Suppression Genes in Women at High Risk of Developing Breast Cancer

QM-MSP, Ki-67, and Cytomorphology of RPFNA Specimens From High Risk Women

University of Alabama at Birmingham

Avon Foundation

National Cancer Institute (NCI)

Johns Hopkins University

Carol Fabian, MD

Professor, Director Breast Cancer Prevention Unit

Fibrinolytic Agents

Anticoagulants

Antibodies

Antibodies, Monoclonal

Heparin

Immunoglobulins

Calcium heparin

Collection of a sample of tumor tissue and a sample of adjacent or counter lateral healthy tissue (if possible) from the surgical room

Collection of a 30mL peripheral blood sample in heparin at several times: during surgical and medical treatment (before surgery, before the start of mAbs and after mAbs)

Blood sampling

Laurence ZITVOGEL, MD, PhD

Agathe DUBUISSON, PhD

Multicentric interventional prospective study with collection of biological samples as part of a routine care research

Ex-vivo Evaluation of the Reactivity of the Immune Infiltrate of Cancers to Treatments With Monoclonal Antibodies Targeting the Immunomodulatory Pathways

Immunophenotyping analysis by flow cytometry (Cyan, Beckman Coulter): identification of several immune sub-populations (T-B-NK lymphocytes, myeloid and tumor cells); identifications of several receptors and ligands (PD1 / PDL1, Tim-3 / HAVCR2,, CTLA-4, 4-1BB / 4-1BBL, Fas / FasL, TRAIL, OX40 / OX40L, ICOS / ICOSL, CD69, CD25 / CD127, NKp46 / NKp30, NKG2D / NKG2DL, galectin-9, MHC class I and II, B7H3 / B7H6); identification of memory subpopulations (CD45RA / CD27 / CCR7) and, if available, intra-cytoplasmic labeling (CXCR3, CCR6, Granzyme B, KI67, TNFα IFNg, IL-17 and IL-21).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma: The NORDIC-SUN-Trial	NCT03977571	Kidney Cancer Renal Cell Carc... Synchronous Neo...	Cytoreductive n... Tissue sampling	18 Years -	University of Aarhus
Endoscopic Characteristics of Duodenal and Ampullary Lesions	NCT01556399	Duodenal Diseas...	Tissue Sampling	18 Years - 85 Years	Western Sydney Local Health District
Protocol to Examine Methylation of Tumor Suppression Genes in Women at High Risk of Developing Breast Cancer	NCT00323908	Breast Cancer		18 Years -	University of Kansas Medical Center
Ex-vivo Evaluation of the Reactivity of the Immune Infiltrate of Cancers to Treatments With Monoclonal Antibodies Targeting the Immunomodulatory Pathways	NCT04349293	Cancer	Tissue sampling Blood sampling	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris
Protocol to Examine Methylation of Tumor Suppression Genes in Women at High Risk of Developing Breast Cancer	NCT00323908	Breast Cancer		18 Years -	University of Kansas Medical Center
Endoscopic Characteristics of Duodenal and Ampullary Lesions	NCT01556399	Duodenal Diseas...	Tissue Sampling	18 Years - 85 Years	Western Sydney Local Health District
Ex-vivo Evaluation of the Reactivity of the Immune Infiltrate of Cancers to Treatments With Monoclonal Antibodies Targeting the Immunomodulatory Pathways	NCT04349293	Cancer	Tissue sampling Blood sampling	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris

Spots Global Cancer Trial Database for tissue sampling