Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Melanoma

Disease Progression

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

Antiemetics

Dermatologic Agents

Gastrointestinal Agents

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Ondansetron

Cyclophosphamide

Immunomodulating Agents

Ipilimumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Treatment:

Cyclophosphamide 300 mg/m2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Nina Bhardwaj, MD,PhD

The purpose of this study is to see whether the combination of low-dose Cyclophosphamide and Anti-CTLA4 (Ipilimumab) will stop tumor growth in patients with advanced skin cancer. The investigators expect to see an increase in response rate of the combination over Anti-CTLA-4 alone and estimate a response rate of approximately 20 % in the proposed population.

The transient removal of CTLA-4-mediated inhibition (CTLA-4 blockade) can induce effective anti-tumor immunity. Efficacy of CTLA-4 blockade as a single agent has been shown in melanoma 53. It has been hypothesized that anti-CTLA-4 antibody might deplete Treg cells 54, inducing autoimmunity. However, patients receiving Ipilimumab have not shown a decrease in Treg number or function in peripheral blood 55.

This trial will answer the question if the combination of Anti-CTLA 4 (following a well established regimen of Ipilimumab) and Cyclophosphamide (given at immunomodulatory doses) will result in antitumor activity in patients with metastatic melanoma due to synergistic immunomodulating effects by overcoming tolerance.

CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma

Phase II Study of CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma

One of the tumor punch biopsy will be put in formalin for paraffin-embedding. The other tumor punch biopsy will be processed to obtain lysates to be used as antigens for the T cell assays. Two tumor punch biopsies (4mm in diameter) will be obtained before and after therapy (baseline and week 12, and optional during weeks 24, 36, and 48) if patients have accessible tumors.

Objective response rate (ORR) using mWHO RC. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Progression-free survival is measured from date of entry to date of 1st documented evidence of recurrence, confirmation of PD, or death (whichever is 1st). T regulatory cells are measured on D1 (pre CTX) \& D3 of each cycle.

Peripheral blood taken at baseline/various therapeutic time points/possibly maintenance cycles to evaluate T regulatory cells identified, serially monitored by polychromatic flow cytometry using FoxP3+/CD4+/CD127low/CD25hi markers.

Bristol-Myers Squibb

Icahn School of Medicine at Mount Sinai

Director, Tumor Vaccine Program

Treatment:

Cyclophosphamide 300 mg/m\^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimuab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Cyclophosphamide, Ipilimumab

Treatment:

Cyclophosphamide 300 mg/m\^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Age, Continuous

Sex: Female, Male

Cutaneous MM

Ocular MM

Unknown Primary MM

Malignant Melanoma (MM) site

Dr. Nina Bhardwaj

Stable disease

Progression of disease

The Anti-tumor Activity of the Combination of Low Dose Cyclophosphamide and CTLA-4 Blockade Using Objective Response Rate (ORR)

Primary Endpoint not met, study terminated, data not collected

Progression-free Survival

Tumor-specific T Cell Responses Will be Measured in a Subset of Patients Who Have Biopsy Accessible Tumor and Have Tumor Biopsies Taken.

T Regulatory Cell Profile in Peripheral Blood

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Nervous System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Hypoxia

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Vasodilator Agents

Nitroglycerin

Patients who received WBRT and the addition 36 mg of transdermal nitroglycerin (TN) with the release of 10 mg in 24 hours, for 24 hours with a 12-hour rest interval (to avoid saturation of receptors)

Patients who received whole-brain radiotherapy (WBRT) (30 Gy in 10 fractions, in 10 days of treatment)

Patients were randomized 1:1 and allocated to either the control arm who received whole-brain radiotherapy (WBRT) or the experimental arm who received WBRT and the addition 36 mg of transdermal nitroglycerin (TN)

Whole-brain radiotherapy

Background: Whole-brain radiotherapy (WBRT) is the standard treatment for multiple brain metastases (BM), in NSCLC patients who are not candidates for treatment with stereotactic radiation body therapy. Hypoxia has been associated with chemo-radioresistance secondary to Vascular Endothelial Growth Factor Receptor (VEGFR) induced by Hypoxia Induced Factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 alfa in tissues, and this may have anti-angiogenic, pro-apoptotic and anti-efflux effects. In this phase II study, we evaluated the effect of transdermal nitroglycerin (TN) on intracranial progression-free survival (ICPFS), objective response rate (ORR) and overall survival (OS) of NSCLC patients with BM.

Material and methods: We performed an open-label, phase II clinical trial among ninety-six histologically confirmed NSCLC patients with BM. Patients were randomized 1:1 to receive NTG plus WBRT or WBRT alone. ORR and ICPFS were evaluated by MRI by two independent, blinded radio-oncologists.

Non-small cell Lung cancer (NSCLC) is the most frequent type of lung cancer worldwide. Brain metastases (BM) are the most frequent neurological complications related to NSCLC and it is estimated that 20% to 40% of these patients will present them at some point during the progression of their disease, leading to a poor prognosis.

As only a selected group of NSCLC patients with single metastases or small lesions are candidates for surgical resection or SBRT, the standard treatment for multiple BM is whole-brain radiation therapy (WBRT). Although 80% of the patients who receive WRBT can initially respond to treatment, 50% of these patients will have disease progression. This further has been related to genetic and environmental factors that may lead to radio-resistance, which is the capacity of a cell to stand the effects of radiant energy. To face this problem, other options such as chemotherapy or radio-sensitizers have shown slight benefit in terms of progression-free survival (PFS) but not in overall survival (OS).

Different studies have suggested tumor microenvironment (TME) has an important role in treatment response of BM-derived from melanoma and NSCLC. The demand for O2 by tumors during cancer is an unsteady phenomenon, caused by continuous metabolic profile changes, immune response activity, and TME interactions. Hypoxia occurs in most tumors and plays an important role in tumor progression. In NSCLC exists a clear relationship between hypoxia and radioresistance. Hence, there is interest into modulate TME hypoxia to improve treatment response. Hypoxia regulates the expression of genes that encode growth factors such as endothelin-1 (ET-1), growth factor-derived platelets-B (PDGF) and vascular endothelial growth factor (VEGF), as well as genes that regulate the production of gas molecules such as nitric oxide (NO) and carbon monoxide (CO). The hypoxia-inducible factor (HIF) is a transcription factor that regulates the cellular response to hypoxia, functioning as a regulator of oxygen homeostasis. Several studies have shown that over-expression of HIF-1α is capable of inducing resistance to chemotherapy, radiotherapy and decreasing overall survival in NSCLC primary tumors.

The administration of nitric oxide donors, such as nitroglycerin, reduces the tumor resistance related to hypoxia by inducing the direct proteolysis of HIF-1α. In tumor cells increases oxygen pressure, increased blood flow, activation of p53 and apoptosis have shown a synergistic effect with ionizing irradiation in an experimental model. According to several randomized phase II studies, the addition of transdermal nitroglycerin to vinorelbine and cisplatin treatment can significantly improve the OS and time to progression in patients with locally advanced non-small cell lung cancer. However, in phase III the addition of nitroglycerin to carboplatin-based did not show benefit in PFS, OS and health-related quality of life (PMID: 26347110). Therefore, the aim of this study was to assess, if the addition of transdermal NTG to standard WRBT treatment among stage IV NSCLC patients with BM, could have a significant impact in PFS and OS as primary end-point and disease control rate (DCR) and overall response rate (ORR) as secondary endpoints.

METHODS Experimental design We conducted a phase II clinical trial with a parallel design study among patients treated at the Instituto Nacional de Cancerología from January 2014 to May 2017. The Median follows up was 18 months. Patients with histologically confirmed NSCLC and documented BM defined as the presence of one or more intra-axial enhancing lesions on gadolinium-enhanced brain magnetic resonance imaging (MRI) were included. Candidate patients who underwent radiosurgery or surgical resection were excluded.

Sample size. The sample size calculation was estimated for a two-sample proportion difference in ORR for NSCLC patients who received WBRT plus TN. Although in one of our previous studies we found a difference of 40% in ORR among locally advanced NSCLC patients 30, we prefer to be more conservative in our estimations taking into account our different study populations. Thus, our sample estimation assumptions were performed for a difference in ORR (delta) of 30% between population (p1= 25% vs p2= 65%) with a study power was set at 0.80 and the two-sided type I error (alpha) was set as 0.05. Therefore, the estimated sample number is 108 (54 per group). We also add a 5% of extra patients, to prevent the possible loss of patients due to the progression of the disease.

Endpoints. The primary outcome was overall response rate (ORR); Secondary endpoints were disease control rate (DCR), intracranial progression-free survival (ICPFS) and overall survival (OS). The radiographic response was assessed by two independent blinded radiologists according to the Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 by comparing the pre-and post-treatment images. Any in-field tumor progression or the appearance of new malignant lesions denoted progressive disease. ORR was defined as the sum of complete and partial response, whereas DCR was defined as the sum of ORR and stable disease. For PFS, time to event was defined and calculated from the date of randomization until radiographic disease progression, treatment discontinuation due to either unacceptable toxicity death by any cause. For OS, time-to-event was defined as time from randomization until death by any cause or loss to follow-up. Observations for patients who did not experience the event were censored at patient-specific last follow-up. Finally, treatment toxicity was evaluated with CTCAE criteria.

Intervention assignment and informed consent Patients were randomized 1:1 and allocated to either the control arm who received whole-brain radiotherapy (WBRT) (30 Gy in 10 fractions, in 10 days of treatment) or the experimental arm who received WBRT and the addition 36 mg of transdermal nitroglycerin (TN) with release of 10 mg in 24 hours, for 24 hours with a 12-hour rest interval (to avoid saturation of receptors). All patients signed the informed consent letter, prior to any procedure. The project was approved by the local scientific and bioethics committee (number). Further details can be found in clinicaltrials.gov (NCT¿?). Patients received chemotherapy (CT) platinum-based or TKI according to mutation status.

Response assessment BM was documented among all patients at NSCLC diagnosis and staging by either computed tomography (CT) of the head gadolinium-enhanced brain magnetic resonance imaging (MRI) at baseline. Then, all patients underwent an MRI prior to treatment and at the end of treatment (median 15 days). The imaging studies were carried out in a Signa HDxt 1.5 T scanner (GE Healthcare). They include conventional sequences in multiple planes, T1, T2, T2 Flair, Echo gradient, Diffusion, volumetric acquisition in axial plane T1 Spoiled Gradient recalled (SPGR), without contrast and after this (Gadolinium). Cerebral perfusion was evaluated by echo-planar sequence with the following parameters: multiphase (25 - 45 phases) with an acquisition time of 1:10, with a PSI of 5 and a flow rate of 5; with a volume of 15ml of gadolinium (+) 20ml of saline at a speed of 5ml/second.

The radiographic response of intracranial tumors was assessed by two blinded and independent blinded radio-oncologist (MY \& FM) according to the Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1 by comparing the pre-and post-treatment intracranial images \[15\]. Any in-field tumor progression or the appearance of new malignant lesions denoted progressive disease. Objective response was defined as the sum of complete and partial response.

DNA Extraction Biopsies were taken using CT-guided tru-cut or bronchoscopy and were analyzed by the pathology department for their histologic diagnosis and neoplastic cellularity quantification (\>50%); they were later embedded in paraffin until processed for DNA extraction. Genomic DNA was extracted from the areas of paraffin slides using a standard procedure and a QIAamp DNA FFPE tissue kit (TMQIAGEN), following manufacturer's instructions.

Determination of EGFR and KRAS mutational status EGFR exon 19, exon 20 and exon 21 gene mutations were detected using the Therascreen RGQ PCR kit (TMQIAGEN, Scorpions ARMS method), which combines both the ARMS and Scorpions technologies for detecting the mutations by real-time polymerase chain reactions (PCR). Real-time PCR was performed using a Rotor-Gene Q 5plex HRM (TMQIAGEN), following manufacturer's instructions.

Statistical analysis Continuous variables were summarized as arithmetic means or medians, with standard deviation or interquartile range for descriptive purposes according to normal data distribution assessed by means of the Shapiro-Swilk test. Meanwhile, categorical variables were summarized as frequencies and percentages. For dichotomous outcomes (eg. objective response rate (ORR), disease control rate (DCR), the percentage (incidence rate) and 95% CI are presented. Inferential comparisons were made using the T-test or two-way ANOVA for continuous variables and with either Mann-Whitney U test or Kruskall-Wallis test, conforming to the data distribution and a number of groups. The χ2 test or Fisher exact test was used for assessing the statistical significance of categorical variables. To address the effect of treatment of secondary outcomes (eg. OS, ICPFS) we performed univariate survival analysis. Time-to-event was estimated using the Kaplan-Meier method and comparisons among the subgroups were analyzed using the log-rank test. For survival curve analysis, all the variables were dichotomized according to their median. After we performed a forward stepwise Multivariable Cox regression model and hazard ratios (HR) were calculated along with their corresponding 95% CIs as a measure of association. Statistically and clinically significant and borderline significant variables (p \<.10) were included for the adjustment in the multivariate Cox regression model. Significantly Kaplan-Meir curves were plotted. Statistical significance was determined as P \<0.05 using a 2-tailed test. Stata software version 14 was used for all statistical analyses.

We perform an open phase II clinical trial among ninety-six histologically confirmed NSCLC patients with BM.

Patients were randomized 1:1 to received TN plus WBR or only WBR. ICPFS was evaluated by two blinded and independent radio-oncologist with MRI.

Nitroglycerin Plus Intracranial Radiotherapy for Brain Metastases in NSCLC Patients

Nitroglycerin Plus Whole Intracranial Radiotherapy for Brain Metastases in Non-small Cell Lung Cancer Patients: a Phase II Open Randomized Clinical Trial

The concurrent administration of nitroglycerin plus chemotherapy and radiotherapy could increases the therapeutic response (ORR, PFS) and OS in patients with NSCLC and cerebral metastases.

Instituto Nacional de Cancerologia de Mexico

MD MSc

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Patients with locally advanced unresectable pancreatic cancer without invasion of the gastrointestinal tract, cT4N0-2M0 Stage III (AJCC/UICC Version 8).

Patients with locally advanced unresectable pancreatic cancer without invasion of gastrointestinal tract will received ablative carbon ion radiotherapy. The prescription dose for primary pancreatic lesion, positive lymph node, and retroperitoneal high-risk recurrence area is 67.5 Gy (RBE weighted dose) in 15 fractions for 3 weeks; Pancreatic primary lesion and positive lymph node SIB to 75 Gy (RBE weighted dose) in 15 fractions for 3 weeks.

Carbon ion radiotherapy

Zheng Wang, MD, PhD

Guo-Liang Jiang, MD

Zheng Wang, MD

Xin Cai, MD

The aim of this study is to investigate the clinical efficacy and safety of ablative carbon ion radiotherapy for locally advanced unresectable pancreatic cancer with pencil beam scanning and simultaneous integrated boost (SIB) technology.

The aim of this study is to investigate the clinical efficacy and safety of ablative carbon ion radiotherapy for locally advanced unresectable pancreatic cancer using pencil beam scanning and simultaneous integrated boost technology with respect to toxicity and tumor control. All enrolled patients will receive carbon ion radiotherapy for the primary pancreatic lesions, positive lymph nodes, and retroperitoneal high-risk recurrence areas. The prescription dose for primary pancreatic lesion, positive lymph node, and retroperitoneal high-risk recurrence area is 67.5 Gy (RBE weighted dose) in 15 fractions for 3 weeks; Pancreatic primary lesion and positive lymph node SIB to 75 Gy (RBE weighted dose) in 15 fractions for 3 weeks. The primary endpoint is 2-year cumulative local regional progression rate (LRP), and the secondary endpoint is to assess the overall survival (OS) and toxicities. Toxicity was assessed using the Common Adverse Event Evaluation Criteria (CTCAE) Version 5.0, and safety and toxicity will be assessed by clinical examination, laboratory examination, and imaging (including CT, MRI, and/or PET/CT).

Radiation: carbon ion radiotherapy for tumors without invasion of GI

Ablative Carbon Ion Radiotherapy With Pencil Beam Scanning for Locally Advanced Unresectable Pancreatic Cancer

Prospective Phase II Clinical Trial of Ablative Carbon Ion Radiotherapy With Pencil Beam Scanning Using Simultaneous Integrated Boost for Locally Advanced Unresectable Pancreatic Cancer

LRP was defined as the percentage of patients with local disease progression (within irradiated area) in the intentional population.

OS was defined as the percentage of patients dead in the intentional population.

Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Safety and toxicity will be assessed by clinical examination, laboratory examination, and imaging (including CT, MRI, and/or PET/CT).

Shanghai Proton and Heavy Ion Center

Principal Investigator

Musculoskeletal Diseases

Contracture

Dupuytren Contracture

Fibroma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Muscular Diseases

Connective Tissue Diseases

Anti-Inflammatory Agents

Adalimumab

Tumor Necrosis Factor Inhibitors

Saline

Jagdeep Nanchahal, PhD FRCS

Dupuytren's disease is a very common condition, affecting 4% of the general UK and US population. It causes the fingers to curl irreversibly into the palm and can be extremely disabling. The disease usually starts as a small firm lump (nodule) in the palm, and in about 40% of patients advances to form cords that pull the fingers into the palm. There is no approved treatment for the early stage of disease. Once patients have established deformities, the diseased tissue can removed by surgery or cut using less invasive techniques such as a needle or an enzyme. However, recovery following surgery usually takes several months and recurrence rates with the less invasive techniques are high.

The investigators have unravelled the cellular process that initiates and maintains the disease progress and identified tumour necrosis factor (TNF) as a new target for treatment. Based on these findings the investigators plan to test the effects of adalimumab, an anti-TNF drug which currently approved for use in patients with rheumatoid arthritis and other inflammatory conditions. The aim of the study is to find out whether treatment by injection with adalimumab directly into the diseased tissue will control the advance of early Dupuytren's disease better than a placebo injection with normal saline.

The investigators will first carry out a small trial in up to 40 patients with established disease to determine the best dose that reduces the activity of the cells responsible for the disorder (Dose Response study). In this part patients who will be having surgery to remove their diseased tissue will receive a single injection of adalimumab into the nodule in their hand about 2 weeks before surgery. The tissue that is then removed during surgery will be analysed in the investigator's laboratories to determine the effect of the drug on the tissue. Patients will be followed for 12 weeks after surgery.

In the second part of the study the investigators will assess whether the optimal dose of the drug prevents early disease advancing in 138 patients (Early Disease study). Patients who take part in the second part of the study will receive a total of 4 injections of adalimumab into the nodule in their hand at three monthly intervals. They will then be checked at 3 \& 9 months after the last injection. In additional to assessing the effect of the injections on the nodule and hand function, information will also be collected to assess the cost effectiveness of the treatment.

During Dose Response part of the trial the Investigator will be blinded. During the Early Disease part of the trial the Investigator will not be blinded but will not carry out any outcome assessments.

Repurposing Anti-TNF for Treating Dupuytren's Disease

A Multi-centre, Double Blind, Randomised, Placebo-controlled, Parallel Group, Phase II Trial to Determine the Efficacy of Intra-nodular Injection of Anti-TNF to Control Disease Progression in Early Dupuytren's Disease, With a Dose Response.

Patient-completed questionnaire: numeric rating scale

Patient completed questionnaire about health \& social care and financial costs of Dupuytren's disease

Assessment of the injection site for pre-specified Adverse Events; surgery site assessment (Dose response only): wound assessment criteria, Centres for Disease Control and Prevention.

Participant identified activity most restricted by DD scored on a scale of 1-10

Department of Health, United Kingdom

Wellcome Trust

180 Therapeutics LP

University of Oxford

Carcinoma

Carcinoma, Squamous Cell

Breast Neoplasms

Squamous Cell Carcinoma of Head and Neck

Carcinoma, Basal Cell

Sarcoma

Neoplasms, Basal Cell

Neoplasms, Glandular and Epithelial

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Soft Tissue Sarcoma

Anti-Infective Agents

Poly ICLC

Interferons

Enrolled patients will receive two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle.

Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks.

Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms.

Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan.

Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks.

Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms.

Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation.

Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy

Follow Up via phone every 3 months for 30months, after completion of treatments.

Poly-ICLC

Nina Bhardwaj, MD, PhD

The purpose of this study is to test the safety of a course of injections containing Poly-ICLC in patients with advanced solid tumors that can be easily and safely reached with a needle.

Poly-ICLC is a compound that has been used to help the body in its fight against cancer.

We hypothesize that this therapeutic in-situ autovaccination strategy is comprised of three immunomodulatory steps. The first is the innate immune local tumor killing induced by intratumoral Hiltonol (via NK, TNF, etc). A very close second step is optimal Th1-weighted priming through the in-situ combination of the poly-ICLC danger signal with the tumor antigens released in step 1 and further processed and cross-presented by poly-ICLC activated mDC, etc. The repeated administration of the Hiltonol danger signal IT in the context of the patient's own tumor antigens and in a way that mimics a natural viral infection may be critical to this step. Once the system is optimally primed, the third step is targeting and maintenance of the immune response and its facilitation at remote tumor sites with IM poly-ICLC through chemokine release, inflammasome activation and other costimulatory factors.

Treatment of Solid Tumors With Intratumoral Hiltonol® (Poly-ICLC)

Treatment of Solid Tumors With Intratumoral Hiltonol® (Poly-ICLC): A Phase II Clinical Study

Patients who are alive on the date of closing follow-up, or 30 months after completing all study treatments, will be censored on that date

Progression-free survival defined as the time in weeks from study entry until tumor progression defined using the Wolchok criteria or death. Patients who are alive and free from progression on the date of closing follow-up will be censored on that date.

In order to minimize the potential for misdiagnosis of pseudoprogression, related to early inflammation, tumor measurement for determination of progression will be made at the earliest at 26 weeks.

Induction of innate and/or an adaptive, specific anti-tumor T cell immune response in the injected tumor lesion and also systemically.

Oncovir, Inc.

Nina Bhardwaj

Director, Immunotherapy Program

Enrolled patients received two cycles of Poly-ICLC treatment. Each priming (intratumoral injections - IT) and boosting (intramuscular injections - IM) treatment course will constitute one cycle.

Poly-ICLC: Cycle 1-Weeks 1 and 2: 1mg Poly-ICLC intratumoral (IT) injections (t=6) into same lesion over 2 weeks.

Weeks 3-9: 1mg Poly-ICLC 2x/week intramuscularly (IM) into thighs or upper arms.

Week 10: No treatment. CT scan of chest, abdomen, pelvis and extremities or neck; possible MRI brain scan.

Cycle 2-Weeks 11 and 12: 1mg Poly-ICLC IT injections (t=6) into same lesion over 2 weeks.

Weeks 13-19 - 1mg Poly-ICLC 2x/weekly IM in thighs or upper arms. Weeks 20-26: no treatment. Week 26, evaluate response in absence of inflammation.

Maintenance - Weeks 27-36: For patients with stable disease or response; IM poly-ICLC injections; evaluation of clinical and immune response. Week 38 repeat tumor assessment, optional biopsy

Participants With Stage 4 Cancer

study terminated early, data not collected. study terminated before all study visits completed. this 24 month visit was not done.

Therapeutic Effect in Treated Patients

Overall Survival in Treated Patients

IT and IM Injections Poly-ICLC

Physical activity and fitness will be assessed objectively with a smartphone

Objective measurement of physical activity and fitness

Henk MW Verheul, MD, PhD

Rationale:

Optimal selection of patients with cancer eligible for a clinical trial, is of utmost importance, but can be very difficult. Patients must be sufficiently fit and have a reasonable life expectancy, to be eligible for participation in clinical trials. In current clinical practice, the ECOG/WHO performance status, is used to select patients for clinical trials, and it has proven to be an independent predictor of survival in patients with cancer. This score is based on a subjective assessment of the treating physician, which can, together with the strong motivation of some patients to participate, lead to overestimation of a patient's actual physical condition and may thereby contribute to early trial discontinuation. Participation of these patients may not only harm them, but will also hamper trial conduct and outcomes.

Both, physical activity and fitness are positively associated with survival in patients with cancer. This gives rise to the investigators hypothesis that objective measurements can be of added value in the selection process. Additionally, preliminary results in 50 patients with cancer that participated in part 1 of the "Counting Steps!" project revealed that the smartphone can produce valid and reliable assessments of physical activity and fitness, and the user friendliness was rated "good" by patients.

The investigators hypothesize that measurements of physical activity and fitness with smartphones will provide more objective and accurate information about the actual physical condition of a patient with cancer.

With a better prediction of trial feasibility (without early trial discontinuation) and overall survival in patients participating in phase I-II clinical trials, the selection of eligible trial participants could be improved. In this way, it is possible to more adequately identify patients who are most likely to successfully participate in a clinical trial and thereby have the highest chance to benefit from trial participation. Successful trial participation will provide optimal palliative care to patients and improve their quality of life. In addition, it may prohibit participation of patients who are currently incorrectly included in clinical trials and suffer from toxic therapies without having a chance to benefit from treatment. A better selection of patients will be beneficial for the trial outcomes and subsequently for the development of new anticancer drugs or treatment regimens.

Objective:

The investigators aim to:

1. Identify whether objective smartphone measurements of physical activity and fitness is predictive for trial feasibility (without early trial discontinuation) in patients with cancer participating in phase I-II clinical trials.
2. Evaluate the feasibility and acceptability of the use of the smartphone's objective assessments of physical activity and fitness in clinical practice.

Study design: Observational study

Study population:

• 135 patients with hematologic or solid cancer referred to the VU medical center for participation in phase I-II clinical trials.

Intervention:

In this observational study, patients will not receive an additional intervention.

Main study parameters/endpoints:

Prior to the start of medical treatment, physicians will rate the performance status, and participants will wear a smartphone for one week to measure the daily number of steps, to complete the 6 minute walk test using the smartphone application, and to fill out the 5-item physical function subscale of the EORTC QLQ-C30. These assessments will be repeated after 4 and 8 weeks.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

No extra visits to the hospital will be necessary. Participation in this study will not cause any additional risks or expected benefits for participants. It will only deliver knowledge, which may be used in the future to better select patients eligible for participation in phase I-II clinical trials or even for regular treatment. Participation in the study will only cost time for patients. The patients will be asked to wear a smartphone for a week, have to perform a six-minute walk test (6MWT) once in this week and have to complete a questionnaire about their own physical function once. Subsequently, patients will repeat those measurements 4 and 8 weeks after inclusion in the phase I-II clinical trial.

Counting Steps! Integration of Objectively Assessed Physical Activity and Fitness With Smartphones in Clinical Oncology Practice.

Early trial discontinuation is defined as discontinuation of trial in the first two months after inclusion, dichotomized into yes or no

Overall survival is defined as the time between start of trial participation and death of any cause and will be tracked via the registration of the original clinical trial

Progression free survival is defined as the time between trial participation and the clinically or radiologically confirmation of progressive disease (established via RECIST-criteria) as defined by the original clinical trial and will be tracked via the registration of the original clinical trial

Amsterdam UMC, location VUmc

Triple Negative Breast Neoplasms

Breast Diseases

Carboplatin

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Combination of liposomal doxorubicin 30milligrams per square meter (mg/m2) and carboplatin area under the curve 5 (AUC 5), administered every four weeks for four cycles.

Participants with triple-negative breast cancer (TNBC):

1. Completed breast surgery and sentinel lymph node biopsy
2. Tumor size less than2.5 and NO/ N1mi disease

Combination of liposomal doxorubicin 30 milligrams per square meter and carboplatin (area under the curve 5), administered every 4 weeks for 4 cycles.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma	NCT01740401	Melanoma	Cyclophosphamid...	18 Years -	Icahn School of Medicine at Mount Sinai
Nitroglycerin Plus Intracranial Radiotherapy for Brain Metastases in NSCLC Patients	NCT04338867	Phase II Clinic... Ninety-six Hist... Randomized 1:1 ... ICPFS Evaluated...	Whole-brain rad...	18 Years - 90 Years	Instituto Nacional de Cancerologia de Mexico
Ablative Carbon Ion Radiotherapy With Pencil Beam Scanning for Locally Advanced Unresectable Pancreatic Cancer	NCT05424159	Pancreatic Canc...	Carbon ion radi...	18 Years - 80 Years	Shanghai Proton and Heavy Ion Center
Nitroglycerin Plus Intracranial Radiotherapy for Brain Metastases in NSCLC Patients	NCT04338867	Phase II Clinic... Ninety-six Hist... Randomized 1:1 ... ICPFS Evaluated...	Whole-brain rad...	18 Years - 90 Years	Instituto Nacional de Cancerologia de Mexico
CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma	NCT01740401	Melanoma	Cyclophosphamid...	18 Years -	Icahn School of Medicine at Mount Sinai
Repurposing Anti-TNF for Treating Dupuytren's Disease	NCT03180957	Dupuytren's Dis...	Adalimumab Saline	18 Years -	University of Oxford
Treatment of Solid Tumors With Intratumoral Hiltonol® (Poly-ICLC)	NCT01984892	Melanoma Squamous Cell C... Squamous Cell C... Sarcoma of the ... Basal Cell Canc... Breast Cancer	Poly-ICLC	14 Years -	Icahn School of Medicine at Mount Sinai
Counting Steps! Integration of Objectively Assessed Physical Activity and Fitness With Smartphones in Clinical Oncology Practice.	NCT03493672	Neoplasms	Objective measu...	18 Years -	Amsterdam UMC, location VUmc
Ablative Carbon Ion Radiotherapy With Pencil Beam Scanning for Locally Advanced Unresectable Pancreatic Cancer	NCT05424159	Pancreatic Canc...	Carbon ion radi...	18 Years - 80 Years	Shanghai Proton and Heavy Ion Center
Nitroglycerin Plus Intracranial Radiotherapy for Brain Metastases in NSCLC Patients	NCT04338867	Phase II Clinic... Ninety-six Hist... Randomized 1:1 ... ICPFS Evaluated...	Whole-brain rad...	18 Years - 90 Years	Instituto Nacional de Cancerologia de Mexico
OCTANE: Adjuvant Liposomal Doxorubicin and Carboplatin for Early-stage Triple-negative Breast Cancer	NCT05949021	Triple Negative...	Combination of ...	-	Rutgers, The State University of New Jersey

Spots Global Cancer Trial Database for phase ii clinical trial