Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Vasoconstrictor Agents

Respiratory System Agents

Central Nervous System Stimulants

Pembrolizumab

Immunomodulating Agents

Nivolumab

Oxymetazoline

Immunologic Factors

Adrenergic Agents

Adrenergic alpha-Agonists

Adrenergic Agonists

Neurotransmitter Agents

Sympathomimetics

Ephedrine

Pseudoephedrine

Nasal Decongestants

Non mutated (BRAF or NRAS) stage II, III or IV (resected) melanoma patients treated with first line adjuvant immunotherapy (anti-PD-1 with either pembrolizumab or nivolumab)

BRAF-mutated stage II, III or IV (resected) melanoma patients treated with first line adjuvant immunotherapy (anti-PD-1 with either pembrolizumab or nivolumab)

NRAS-mutated (BRAF or NRAS) stage II, III or IV (resected) melanoma patients treated with first line adjuvant immunotherapy (anti-PD-1 with either pembrolizumab or nivolumab)

* Frequency of relapse to adjuvant immunotherapy according to clinical features
* Duration of relapse as defined by the time (days) between adjuvant immunotherapy onset and relapse date according to clinical features

Frequency and duration of response to adjuvant immunotherapy according to clinical features

Percentages of each type of relapse (i. e. local, distant, unique or multiple) according to clinical features

Frequency of each type of relapse (i. e. local, distant, unique or multiple) to adjuvant therapy according to clinical features

Duration of relapse-free survival as defined by the time (days) between adjuvant immunotherapy onset and relapse date.

Duration of relapse-free survival according to clinical features

Duration of relapse-free survival as defined by the time (days) between adjuvant immunotherapy onset and the date of death (irrespectively of the cause) 10 years after inclusion in the study. Alive or lost to follow-up patients will be censored at the date of the last follow-up visit.

Duration of overall survival according to clinical features

Response rate to adjuvant immunotherapy and to treatment lines subsequent to relapse. Response rate to adjuvant immunotherapy is defined by the absence of relapse as assessed by the physician following the first year of adjuvant therapy. Response to treatment after relapse is defined as partial or complete response as assessed by the physician following the first year of adjuvant therapy.

Overall response rate

Rate of adverse events according to their nature and grade (as defined by CTCAE V 5.0) and according to clinical features

Frequency of adverse events according to clinical features

Stéphane Dalle, PhD

Stéphane Dalle, MD, PhD

Surgical excision is the treatment of choice for stage II, III and resectable stage IV melanoma and is curative in most cases. Given the recent success of immunotherapy for the treatment of patients with advanced metastatic melanoma, the use of immunotherapy has been evaluated in the adjuvant setting for patients at high risk of recurrence. In this context, Nivolumab prolonged Recurrence-Free Survival (RFS) while reducing toxicity compared with Ipilimumab in a phase III clinical trial, and was subsequently FDA-approved in December 2017 for adjuvant treatment of locally advanced melanoma with metastatic lymph node involvement after resection of cutaneous lesions. While a fraction of patients benefit from adjuvant PD-1 immunotherapy, approximately 40% of patients are still relapsing despite this adjuvant treatment, without being able to identify them early and with poor understanding of resistance mechanisms. Additionally, about 15% of the patients will develop serious adverse effects driven by immunotherapy and often discontinuing or even contraindicating the onset of subsequent treatments, hence affecting global patients care. It is therefore of prime importance to identify clinical features able to predict response and toxicities to adjuvant immunotherapy in melanoma.

Predictive Clinical Features for Response to Adjuvant Immunotherapy in Stage II,III and IV Resected Melanoma

• Duration of response as defined by the time (days) between adjuvant immunotherapy onset and relapse date according to clinical features.

Hospices Civils de Lyon

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

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

Anti-Infective Agents

Analgesics

Interferons

Interleukin-2

Interferon-alpha

Interferon alpha-2

Antiviral Agents

Analgesics, Non-Narcotic

Immunotherapy with interferon-alpha and interleukin

Interferon Alfa-2a in combination with Interleukin

Interferon Alfa-2a

Rodolfo Passalacqua, Medicine

Carlo Buzio, Medicine

The aim of this study is to compare the efficacy (in terms of event-free survival and overall survival) of an adjuvant therapy with IFN-alpha plus low-dose of IL2 vs a wait-and-see program in patient with radically operated renal cell carcinoma.

For pts with non-metastatic RCC, no standard adjuvant treatment exists. Immunotherapy (IT) using IFN and/or IL2 is effective in metastatic disease setting. Low and chronically repeated doses of IL2 plus IFN induce a persistent stimulation of the immune system with no relevant toxicity.

Surgically treated RCC pts were randomized to the following arms: A) low-dose IT; B) control arm. IT consisted of a 4-week cycle of s.c. IL2 (5 days/wk, 1 million UI/sqm bid d 1,2 and 1 million UI/sqm x 1 d 3,4,5) + IFN (1,8 million UI/sqm d 3,5 of each week). Cycles were repeated every 4 months for the first 2 years and every 6 months for the remaining 3 years. Each patient received 12 cycles in 5 years. Inclusion criteria were as follows: histological diagnosis of RCC, age \<75 yrs, radical or partial nephrectomy within the past 3 months, pT1 (diameter of T \> 2,5 cm), T2, T3 a-b-c; pN0-pN3, M0; good cardiac and renal function and no autoimmune disease.

Low-dose IL-2 Plus IFN-alpha Immunotherapy as Adjuvant Treatment of Renal Carcinoma.

Adjuvant Low-dose Interleukin-2 (IL2) Plus Interferone-alpha (IFN) in Operable Renal Cell Cancer (RCC). Phase III, Randomized, Multicenter Trial of the Italian Oncology Group for Clinical Research (GOIRC).

Gruppo Oncologico Italiano di Ricerca Clinica

Digestive System Diseases

Symptoms and General Pathology

Esophageal Neoplasms

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasm, Residual

Neoplastic Processes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Wenbin Shen, PhD

Hesong Wang, PhD

This trial aims to assess changes in minimal residual disease (MRD) status before and after radical concurrent chemoradiotherapy combined with immunotherapy and adjuvant immunotherapy after neoadjuvant immunochemotherapy in patients with inoperable stage II-III esophageal squamous cell cancer (ESCC), and correlate with the efficacy of adjuvant immunotherapy.

Presence of circulating tumor DNA (ctDNA) is indicative for minimal residual disease (MRD) and has high predictive value for efficacy and tumor recurrence. Concurrent chemoradiotherapy becomes the standard of care for unresectable, locally advanced esophageal squamous cell cancer, and the addition of immunotherapy to radiotherapy has been shown to increase efficacy without increasing side effects. The ECMRD-001 trial aims to assess changes in MRD status before and after radical concurrent chemoradiotherapy combined with immunotherapy and adjuvant immunotherapy after neoadjuvant immunochemotherapy in patients with inoperable stage II-III esophageal squamous cell cancer (ESCC). The specimen collection time points were divided into MRD-related blood collections, MRD-related tissue collection, T-cell immunohistobank-related blood collections, and T-cell immunohistobank-related tissue collection before, during, and after treatment and follow-up. Primary endpoint is the relationship between MRD status at different time points and treatment efficacy. Secondary endpoints include the relationship between MRD status and immune microenvironment, radiotherapy dose, and tumor recurrence. Exploratory endpoint is to investigate ctDNA mutations in ESCC patients receiving adjuvant immunotherapy. To the investigators' knowledge, the ECMRD-001 study is the first clinical trial to investigate ctDNA-based MRD guided strategies in stage II-III ESCC patients who receive radical chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy followed by adjuvant immunotherapy. After our research it may be possible to confirm that ctDNA-based MRD may be a predictive marker for the efficacy and tumor recurrence of inoperable ESCC patients; elevated ctDNA-MRD may predict tumor recurrence earlier than imaging; ctDNA-based MRD analysis and ctDNA-based MRD guided diagnosis and treatment may be implemented into clinical practice to improve efficacy and reduce tumor recurrence of inoperable stage II-III ESCC.

The specimen collection time points were divided into MRD-related blood collections, MRD-related tissue collection, T-cell immunohistobank-related blood collections, and T-cell immunohistobank-related tissue collection before, during, and after treatment and follow-up. The investigators will test circulating tumor DNA (ct-DNA) based minimal residual disease (MRD) indicators for research

Minimally Residual of Esophageal Cancer 001

Minimal Residual Disease Guided Radical Chemoradiotherapy Combined With Immunotherapy After Neoadjuvant Immunochemotherapy Followed by Adjuvant Immunotherapy for Esophageal Squamous Cell Cancer

High-frequency mutated genes in the ESCC patients undergoing adjuvant immunotherapy and the corresponding mutation frequency (percentage of samples with mutations out of all samples).

The changes in MRD status before and after radical CCRT combined with immunotherapy and adjuvant immunochemotherapy in patients with inoperable resectable stage II-III ESCC, correlating with the efficacy of adjuvant immunotherapy

Differences in overall survival (OS) and progression-free survival (PFS) between MRD positive and negative patients after neoadjuvant immunochemotherapy. OS is defined as time from start of treatment to death (from any cause). PFS is defined as the time between the start of treatment and the onset of (any aspect of) tumor progression or death (from any cause).

MRD status and T-lymphocyte differences across efficacy responses after receiving radical CCRT combined with immunotherapy. Therapeutic response is evaluated according to immune-related response evaluation criteria in solid tumors (irRECIST).

The differences in MRD status between radiation doses of 50Gy and 60Gy, and the correlation with patient prognosis.

The association between serial changes in MRD status and the efficacy of adjuvant immunotherapy. Therapeutic response is evaluated according to immune-related response evaluation criteria in solid tumors (irRECIST).

The timing of MRD advance warning of recurrence in patients ahead of imaging cues

Hebei Medical University Fourth Hospital

Carcinoma, Transitional Cell

Transitional Cell Carcinoma

Gemcitabine

Carboplatin

Cisplatin

muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant chemotherapy

muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant immunotherapy

cisplatin/carboplatin-gemcitabine 4-6 cycles

Adjuvant chemotherapy

adjuvant immunotherapy

jiwei huang, M.D

In our study, the ultra-deep sequencing of circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) were performed to assess whether ctDNA and utDNA can be used as predictive biomarkers for the detection of minimal residual disease (MRD) and early diagnosis of UTUC recurrence, and explored the role of ctDNA and utDNA detection of MRD in the prediction of adjuvant therapy efficacy and prognostic evaluation.

60% of Upper Urinary Tract Urothelial Carcinoma (UTUC) patients with muscle-invasive disease at diagnosis, which progresses rapidly, aggressively, and has a poor prognosis. Up to 30-40% of the patients may develop bladder recurrance after radical nephroureterectomy for primary upper tract urothelial carcinoma.

Minimal residual disease (MRD) refers to the small number of malignant cells that remain after curative treatments (curative intent surgical resection, radiotherapy, and/or chemotherapy). MRD is common in patients with blood cancer, and is known to be associated with recurrence and poor prognosis. Recent studies also reported that MRD-negative in postoperative solid tumors such as colorectal/colon cancer and muscle-invasive bladder cancer is associated with better survival outcomes. However, the clinical values of MRD monitoring for adjuvant therapy in postoperative UTUC remain inadequate.

A total of 103 patients with stage II-IV UTUC will be recruited in this clinical trial. The following plasma samples, urine samples and tumor tissues will be collected from each patient including 1) preoperative plasma and urine samples; 2) surgical tissue samples; 3) plasma and urine samples 1 month after surgery; 4) plasma and urine samples during adjuvant therapy; and 5) plasma and urine samples after adjuvant therapy; 6) plasma and urine samples in follow-up. In addition, demographic and tumor characteristics of the patients will be collected for subsequent analysis, including age, sex, tumor stage, pathological stage, disease couse time, etc. Tumor tissues and matched peripheral blood were collected before treatment and WES was used ctDNA detection techniques. For each patient, we selected up to 30 clonal somatic mutations for personalized, tumor informed ctDNA assay design.Statistical analyses will be performed to analyze the survival outcomes and to explore the clinical value of MRD monitoring for adjuvant therapy in postoperative UTUC.

Circulating Tumour DNA and Urine Tumor DNA Detection of Minimal Residual Disease in Locally Advanced Upper Tract Urothelial Carcinoma With Radical Nephroureterectomy: A Cohort Study

Ruijin Hospital

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Fudan University

West China Hospital

Xiangya Hospital of Central South University

Peking University First Hospital

Shanghai 10th People's Hospital

The Second Affiliated Hospital of Dalian Medical University

First Affiliated Hospital Xi'an Jiaotong University

The First Affiliated Hospital of Soochow University

Tianjin Medical University Second Hospital

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

The Affiliated Hospital of Medical School of Ningbo University

Yantai Yuhuangding Hospital

Nanjing Medical University Affiliated Cancer Hospital

Zhejiang University

Lihuili Hospital

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Zhongda Hospital

RenJi Hospital

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Micronutrients

Herbal and Botanical

Oxaliplatin

Leucovorin

Fluorouracil

Capecitabine

Cola

After colectomy, patients will accept chemotherapy combined with cytokine-induced killer cells (CIK) therapy synchronously for 6 months.

For CapeOx regimen:

3×109 CIK cells on days 1-3; Oxaliplatin 130mg/m2 on day 7; Capecitabine 1000mg/m2 twice daily on days 7-20; Repeat every 3 weeks for 6-8 cycles.

For mFolfox6 regimen:

Oxaliplatin 85mg/m2 IV over 2 hours on day 1; Leucovorin 400mg/m2 IV over 2 hours on day 1; 5-FU 400mg/m2 IV bolus on day 1, then 2400mg/m2 IV continuous infusion over 46-48 hous; 3×109 CIK cells on days 9-11; Oxaliplatin 85mg/m2 IV over 2 hours on day 15; Leucovorin 400mg/m2 IV over 2 hours on day 15; 5-fluorouracil (5-FU) 400mg/m2 IV bolus on day 15, then 2400mg/m2 IV continuous infusion over 46-48 hours; Repeat every 4 weeks for 5-6 cycles.

After colectomy, patients will accept adjuvant chemotherapy for 6 months, that is 6-8 cycles of CapeOX regimens (the same as those in arm A), or 10-12 cycles of mFolfox6 regimens(the same as those in arm A), followed by 6-8 cycles of cytokine-induced killer cells (CIK) therapy at least 2 weeks later.

After colectomy, patients will accept adjuvant chemotherapy for 6 months, that is 6-8 cycles of CapeOX regimens (the same as those in arm A), or 10-12 cycles of mFolfox6 regimens （the same as those in arm A）.

cytokine-induced killer cells

Yanjuan Zhu

Haibo Zhang, MD

Haibo Zhang

Yong Li

Jianping Bai

Lirong Liu

Yihong Liu

Yanchun Qu

Xin Qu

Jin Wan

It has been reported that the immune status of patients with cancer were suppressed, especially those after surgery and adjuvant chemotherapy. Thus, immunotherapy may decrease the recurrence rate after surgery. CIK cells transfusion has been reported as an effect therapy in advanced cancers. In another retrospective study, investigators found that adjuvant CIK therapy would prolong the disease-free survival (DFS) for colorectal cancer patients.

The purpose of this study is to determine wether adjuvant immunotherapy with CIK cells in patients with colon cancer after operation will prolong DFS, and overall survival (OS).

Efficacy of Adjuvant Cytokine-induced Killer Cells in Colon Cancer

Efficacy of Adjuvant Immunotherapy With Cytokine-induced Killer Cells in Patients With Stage II/III Colon Cancer

Patients who were recurrence free at the end of study or lost to follow-up were censored

Patients who were survival at the end of study or lost to follow-up were censored

Any undesirable secondary effect which occurs in addition to the desired therapeutic effect of CIK or chemotherapy, during the period from the first cycle of chemotherapy or CIK infusion to the end of study. The side effects were described according to the NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events)

During the period of chemotherapy and CIK infusion

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Predictive Clinical Features for Response to Adjuvant Immunotherapy in Stage II,III and IV Resected Melanoma	NCT05527795	Melanoma	Frequency and d... Frequency of ea... Duration of rel... Duration of ove... Overall respons... Frequency of ad...	18 Years -	Hospices Civils de Lyon
Predictive Clinical Features for Response to Adjuvant Immunotherapy in Stage II,III and IV Resected Melanoma	NCT05527795	Melanoma	Frequency and d... Frequency of ea... Duration of rel... Duration of ove... Overall respons... Frequency of ad...	18 Years -	Hospices Civils de Lyon
Low-dose IL-2 Plus IFN-alpha Immunotherapy as Adjuvant Treatment of Renal Carcinoma.	NCT00502034	Carcinoma, Rena...	Interferon Alfa... Interleukin-2	18 Years - 75 Years	Gruppo Oncologico Italiano di Ricerca Clinica
Minimally Residual of Esophageal Cancer 001	NCT05952661	Esophageal Carc... Minimal Residua...		18 Years - 75 Years	Hebei Medical University Fourth Hospital
Circulating Tumour DNA and Urine Tumor DNA Detection of Minimal Residual Disease in Locally Advanced Upper Tract Urothelial Carcinoma With Radical Nephroureterectomy: A Cohort Study	NCT05595408	Muscle Invasive...	Adjuvant chemot... adjuvant immuno...	18 Years -	RenJi Hospital
Efficacy of Adjuvant Cytokine-induced Killer Cells in Colon Cancer	NCT01929499	Colonic Neoplas...	cytokine-induce...	18 Years - 80 Years	Guangdong Provincial Hospital of Traditional Chinese Medicine

Spots Global Cancer Trial Database for adjuvant immunotherapy