Neoplasms

All Conditions

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Melanoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

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Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

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Nevus

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Female Urogenital Diseases and Pregnancy Complications

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Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

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Antineoplastic Agents

Analgesics

All Drugs and Chemicals

Interleukin-2

Boost of radiotherapy + high dose IL-2 treatment: Three daily doses boost radiotherapy at 6-12 Gy to at least 1, and up to a maximum of 5, metastatic fields, will be administrated on days -4 -3 -2 or -3 -2 -1 before the first and the third cycle of IL-2 (Interleukin 2). The first day of administration of IL-2 of each cycle is the day +1.

Treatment with IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV (intravenous) infusion for 72 hours) will start on day +1 and will be administered every 3 weeks up to 4 cycles, than every 3-4 weeks for a further 2 cycles.

Patients will be evaluated every 8 weeks with computed tomography to determine the response, and every 3 months after completion of treatment until death.

Boost of radiotherapy + high dose IL-2 treatment

Oriana Nanni, PhD

Laura Ridolfi, MD

Title: Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with High-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response

Phase: Proof of Principle phase II study

Study Design: Single center, open-label trial to assess the immune response and potential biomarkers predictive of response

Study Duration:

Total duration: 36 months Enrollment: 20 months Treatment: 5 months per patient Follow-up every three months

Number of Subjects:

Mini-max two-stage Simon design:

• Step 1: 7 patients enrolled

If tumor antigen-specific immune response is observed in at least 3 patients:

• Step 2: recruitment of an additional 12 patients

Title: Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with High-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response

Phase: Proof of Principle phase II study

Study Design: Single center, open-label trial to assess the immune response and potential biomarkers predictive of response

Study Duration:

Total duration: 36 months Enrollment: 20 months Treatment: 5 months per patient Follow-up every three months

Primary objectives:

1. to determine the tumor antigen-specific immune response induced by the treatment
2. to prospectively determine the predictive/prognostic value of pretreatment biological features in identifying patients who will benefit from HDIL-2-based therapy

Secondary end points:

1. Toxicity
2. Response Rate
3. Overall Survival.

Number of Subjects:

Mini-max two-stage Simon design:

• Step 1: 7 patients enrolled

If tumor antigen-specific immune response is observed in at least 3 patients:

• Step 2: recruitment of an additional 12 patients

Study Product, Dose, Route, Regimen and duration of administration:

Three daily doses boost radiotherapy (XRT) at 6-12 Gy to at least 1, and up to a maximum of 5, metastatic fields, will be administrated on days -4 -3 -2 or -3 -2 -1 before the first and the third cycle of IL-2. The first day of administration of IL-2 of each cycle is the day +1.

Treatment with IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV infusion for 72 hours) will start on day +1 and will be administered every 3 weeks up to 4 cycles, than every 3-4 weeks for a further 2 cycles.

IL-2 will be withheld for refractory hypotension (hypotension where isotropic or vasoactive therapy is ineffective and that persists despite specific medical therapy set), anuria for \> 24 hours, respiratory distress, confusion, sustained ventricular tachycardia, signs of myocardial ischemia or myocarditis, persistant metabolic acidosis, atrial fibrillation and documented systemic infection.

Patients will be evaluated every 8 weeks with computed tomography to determine the response, and every 3 months after completion of treatment until death (the time of disease progression and the initiation of alternative therapies will also be documented).

Statistical Methodology:

A minimax two-stage Simon design will be employed. A 40% immune response will preclude further study, whereas a 70% response rate will indicate that further study would be warranted. Using alfa and beta errors of 0.10, 7 patients will be enrolled during the first stage, and if an immune response is observed in at least 3 patients the study will go on, and an additional 12 patients will be treated. The treatments will be considered active if a tumor antigen-specific immune response is observed in 11 out of 19 patients treated. The analysis will be performed on an intention to treat population, i.e. all patients having received at least one cycle of therapy.

Radiotherapy as an Immunological Booster in Patients With Metastatic Melanoma or Renal Cell Carcinoma Treated With High-dose Interleukin-2

Radiotherapy as an Immunological Booster in Patients With Metastatic Melanoma or Renal Cell Carcinoma Treated With High-dose Interleukin-2: Evaluation of Biomarkers of Immunologic and Therapeutic Response

Determination of the immunological efficacy of the combined RT (radiotherapy)/HDIL-2 (high dose Interleukin 2) treatment in terms of ability of the treatment to enhance the proportion of circulating immune effectors specific for tumor antigens known to be expressed in RCC (Renal Cell Carcinoma) and/or melanoma

Determination of the predictive value of pretreatment biomarkers in identifying patients who will benefit from combined RT/HDIL-2 treatment

Evaluation of safety and tollerability of the experimental treatment. The percentage of patients reporting an Adverse Event (AE) up to 30 days after HD-IL-2 treatment will be tabulated with 95% confidence intervals, by type of AE. The overall rate of grade 3-4 related AE will be computed.

Evaluation of the response rate of treated patients

Evaluation of the overall survival of treated patients

Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma, Transitional Cell

Lung Neoplasms

Transitional Cell Carcinoma

Vaccines

Dimethyl Sulfoxide

Group A (has not yet started standard treatment) and Group B (has begun standard treatment at least 4 months before first vaccine, and the decease development is status quo) will receive 6 vaccines in total. Firstly 3 vaccines intraperitoneal biweekly and lastly 3 vaccines intramuscular biweekly while the patients are receiving standard immune therapy.

The personalised NPV-ds001 drug substance consists of multiple linear peptides (Pep-Ints) comprising natural L-amino acids dissolved in Dimethyl sulfoxide (DMSO) and 1 ml adjuvants (CAF09b) and 1,08 ml Tris buffer (25 ml).

EVAX-01-CAF09b

Inge Marie Svane, Prof., MD

The primary objective is to assess tolerability and safety of a personalized neo-antigen vaccine containing up to 15 peptides derived from somatic mutation of the individual patient's cancer, with CAF09b as adjuvant. The vaccine formulation will be administered in combination with an approved anti-PD-1 or anti-PD-L1 inhibitor to patients with advanced solid tumors. The endpoint is the characterization of adverse events (AE) assessed by CTCAE 4.0.

The secondary objective is feasibility to manufacture a personalized neo-antigen vaccine within 6 weeks of enrolment with the PIONEER pipeline, and to evaluate the immune response before, during and after treatment with the personalized neo-antigen vaccine. And evaluate the effect on the immune response correlated to dose escalation of peptides in the vaccine. The endpoint is to evaluate the induction of adaptive immune responses to the personalized neo-antigen vaccine measured by functional assays and peptide-MHC multimer stainings.

The tertiary objective is to evaluate the clinical efficacy of the treatment. The endpoints will be objective responses (OR), progression free survival (PFS) and overall survival (OS).

Cancer immunotherapy has shown the ability to improve the survival of patients with multiple types of advanced cancers. The human immune system can recognize the products of somatic genetic alterations in tumors, or neo-antigens, which are not expressed on normal cells. These neoantigens are an attractive immune target because their selective expression on tumors can minimize immune tolerance as well as the risk of side effects such as autoimmune reaction.

Although neoantigens are ideal targets for cancer immunotherapies, most neoantigens arise from unique mutations and are not shared between individual patients. Thus, neoantigen-directed immunotherapy will need to be personalized. Novel technical advances in next-generation sequencing allow fast and systematic prediction of cancer neoantigens for each individual patient. Initial attempts of therapeutic cancer vaccination targeting individual neo-antigens have proven non-toxic and met their immunological endpoints.

In this study investigators will use the proprietary platform PIONEER for fast and accurate identification of a neo-antigen vaccine tailored to each individual patient. The vaccine, based on 5-15 peptides derived from a patient's tumor individual neo-antigens, will be formulated with a novel adjuvant to strengthen CD8+ T cell immunity to cancer. Immune checkpoint inhibitors targeting PD-1 or PD-L1 will be administered both before, during and after vaccination to unleash the activity of vaccine-induced immune responses.

Not a randomized study. 25 patients to be included. Group A) has not yet started standard treatment Group B) has begun standard treatment at least 4 months before first vaccine, and the decease development is status quo.

Personalized Neo-antigen Vaccine in Advanced Solid Tumors (NeoPepVac)

A Pilot Study of the Safety, Tolerability, Feasibility and Efficacy of Anti-PD-1 or Anti-PD-L1 in Combination With a Personalized Neo-antigen Vaccine in Advanced Solid Tumors (NeoPepVac)

Overall survival (OS), defined as the time from the start of treatment to death, will be described with the Kaplan-Meier curve.

Progression-free survival (PFS), defined as the time from start of treatment to disease progression, relapse or death due to any cause, whichever is earlier, will be described with the Kaplan-Meier curve.

Tumor responses will be evaluated using RECIST1.1 for the assessment of efficacy.

The primary objective is to assess tolerability and safety of a personalized neo-antigen vaccine containing up to 15 peptides derived from somatic mutation of the individual patient's cancer, with CAF09b as adjuvant. The vaccine formulation will be administered in combination with an approved anti-PD-1 or anti-PD-L1 inhibitor to patients with advanced solid tumors. The endpoint is the characterization of adverse events (AE) assessed by CTCAE 4.0.

To evaluate the immunological impact of the treatment. Elispot and tetramer staining methods will be applied to identify NeoPepVac specific T cells in the blood over time

Herlev Hospital

Clinical Professor

Antibodies

Antibodies, Monoclonal

Molgramostim

Sargramostim

Tin Fluorides

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

GM-CSF will be administered subcutaneously daily for 14 days in a dose of 125 µg/m2 beginning on D1 of each 21-day cycle for 8 cycles until month 6. Maintenance therapy will begin at month 6 and will consist 14 days of GM-CSF repeated every 3 months for up to 2 years or until disease progression, whichever occurs first.

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

Patients will be treated with 4 courses of ipilimumab administered every 3 weeks intravenously in a dose of 10 mg/kg, with appropriate stopping/de-escalation rules. Maintenance therapy will begin at month 6 and will consist of ipilimumab in the same dose administered at the end of cycle 4 repeated every 3 months for up to 2 years or until disease progression, whichever occurs first.

Lynn E. Spitler, M.D.

The study is an open-label, single arm single Center Phase II study to evaluate the safety and efficacy of the combination of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF, Leukine) and Ipilimumab (Yervoy) as therapy for patients with unresectable metastatic malignant melanoma.

The study is an open-label, single arm single Center Phase II study to evaluate the safety and efficacy of the combination of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF, Leukine) and Ipilimumab (Yervoy) as therapy for patients with unresectable metastatic malignant melanoma. The patient sample will be approximately 43 evaluable individuals, males and females 18 years of age or older with measurable metastatic melanoma. Immunologic testing will be done to evaluate correlation with clinical outcome.

Patients will be treated with 4 courses of GM-CSF and ipilimumab administered every 3 weeks. GM-CSF will be administered subcutaneously daily for 14 days in a dose of 125 µg/m2 beginning on D1 of each 21-day cycle. Ipilimumab intravenously in a dose of 10 mg/kg, with appropriate stopping/de-escalation rules. After the initial 3 months (4 cycles) of treatment, GM-CSF administration will continue for 4 additional cycles on the same schedule and dose without ipilimumab for 14 days every 21 days until month 6. Maintenance therapy will begin at month 6 and will consist of ipilimumab in the same dose administered at the end of cycle 4 combined with 14 days of GM-CSF. Administration of this combination will be repeated every 3 months for up to 2 years or until disease progression, whichever occurs first. During the maintenance phase, GM-CSF will only be administered for 14 days in conjunction with ipilimumab and will not be administered in the intervening time period.

Granulocyte Macrophage-Colony Stimulating Factor and Ipilimumab as Therapy in Melanoma

GM-CSF and Ipilimumab as Therapy in Metastatic Melanoma, a Phase II Study

Disease control rate will be measured at 24 weeks from the start date of protocol therapy using the immune-related Response Criteria (irRC)

Blood will be drawn for immunologic testing at each patient visit.

According to irRC criteria, increase in the size of target lesions or the appearance of new lesions within 12 weeks of the initiation of ipilimumab therapy does not necessarily represent disease progression (as they would using conventional RECIST criteria).

Overall Survival (OS) is defined as the time from the date of the first treatment dose to date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the patient was known to be alive.

The Objective Response Rate (RR) at any time during the 2 years of study treatment will be evaluated in this study using the immune related Response Criteria (irRC).

The Time to Objective response is defined as the time from the date of the first treatment dose to the date of first documentation of disease response.

The duration of objective response (CR or PR) will be measured from the date the response was first documented to the date of progression or death due to progressive disease, whichever occurs first.

The safety of the combination as defined by the NCI CTCAE criteria, Version 4.0.

University of California, San Francisco

Lynn E. Spitler, MD

Director

Pembrolizumab

Subjects will receive WB-DW MRI and FLT PET to assess disease burden after receiving pembrolizumab.

Each patient will receive pembrolizumab 200mg administered as a 30 minute intravenous (IV) infusion every 3 weeks for an indefinite period.

FLT PET/CT is increasingly being utilized as an early PD biomarker in cancer given the close association between FLT uptake and proliferative index.

FLT PET

Yvonne Saenger, MD

The purpose of this study is to test two imaging techniques, one called whole body (WB) diffusion weighted (DWI) magnetic resonance imaging (MRI) (WB-DWI MRI), and another called Fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography (PET) (F-18-FLT PET). The goal is to see whether these imaging techniques would allow the study doctors to see changes in the size of a tumor earlier for patients with metastatic melanoma receiving Pembrolizumab (MK-3475).

There is a growing body of evidence that demonstrates that tumor proliferation, measured classically by immunohistochemical evidence of increased Ki-67 expression, can be reliably determined in vivo using radiolabeled thymidine. The development of \[18F\]-fluorothymidine (FLT) PET has been reliably identified as a marker of cellular proliferation, and has been shown to identify changes in proliferation in successfully treated patients.

MRI and PET to Assess Pembrolizumab Response

A Feasibility Study of MRI and PET Imaging to Assess Response to MK-3475 (Pembrolizumab) in Patients With Metastatic Melanoma

Sensitivity of WB-DW MRI and FLT-PET imaging in lesion detection and evaluation for metastatic melanoma.

Lesion metrics including diameter and intensity as measured by FLT-PET and WB-DWI MRI will be compared with standard RECIST and volumetric criteria as well as Immune Response Criteria (IRC).

Assessed by programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and programmed death-ligand 2 (PD-L2) expression, quantification of infiltrating cluster of differentiation 8 (CD8+) T cells at the invasive margin and within the center of the tumor, and assessment of cluster of differentiation 2 (CD2) expression. Formalin fixed paraffin embedded sections will be used. Cluster of differentiation 3 (CD3) and CD8 will be stained for and the immunoscore will be calculated using standard methods.

Assessed by NanoString with measurement of immune related genes. Expression levels will be compared pre-treatment and post-treatment.

Index lesions identified on the baseline standard Response Evaluation Criteria In Solid Tumors (RECIST) image set will be evaluated for changes in FLT maximum standardized uptake value (SUVmax) and standardized uptake volume (SUVvol), and changes in antibody-drug conjugate (ADC) on DWI MRI at 6 weeks compared with baseline. These early response measures will then be compared with RECIST response measurements on conventional imaging.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Radiotherapy as an Immunological Booster in Patients With Metastatic Melanoma or Renal Cell Carcinoma Treated With High-dose Interleukin-2	NCT01884961	Metastatic Rena... Malignant Melan...	Boost of radiot...	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Personalized Neo-antigen Vaccine in Advanced Solid Tumors (NeoPepVac)	NCT03715985	Malignant Melan... Non Small Cell ... Bladder Urothel...	EVAX-01-CAF09b	18 Years - 120 Years	Herlev Hospital
Granulocyte Macrophage-Colony Stimulating Factor and Ipilimumab as Therapy in Melanoma	NCT01363206	Malignant Melan...	Granulocyte-Mac... Ipilimumab	18 Years -	Northern California Melanoma Center
Radiotherapy as an Immunological Booster in Patients With Metastatic Melanoma or Renal Cell Carcinoma Treated With High-dose Interleukin-2	NCT01884961	Metastatic Rena... Malignant Melan...	Boost of radiot...	18 Years -	Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Granulocyte Macrophage-Colony Stimulating Factor and Ipilimumab as Therapy in Melanoma	NCT01363206	Malignant Melan...	Granulocyte-Mac... Ipilimumab	18 Years -	Northern California Melanoma Center
MRI and PET to Assess Pembrolizumab Response	NCT02591654	Malignant Melan...	Pembrolizumab FLT PET	18 Years -	Columbia University

Spots Global Cancer Trial Database for malignant melanoma, metastatic