Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, T-Cell, Cutaneous

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

* Patients with plaque or tumor skin lesions of cutaneous T cell lymphoma or peripheral T cell lymphoma
* Mandatory skin biopsy for corollary studies will be obtained
* Patients will undergo percutaneous placement of four total microdevice(s) into two skin lesions (2 MD per skin lesion)

* Only patients with plaque or tumor skin lesions of cutaneous T cell lymphoma or peripheral T cell lymphoma who plan to start systemic therapy as part of standard of care
* Mandatory skin biopsy for corollary studies will be obtained
* Patients will undergo percutaneous placement of four total microdevice(s) into two skin lesions (2 MD per skin lesion)
* Participants will receive standard of care therapy and clinical course followed
* Participants will undergo standard of care therapy as previously determined by treating oncologist and/or dermatologist prior to enrollment to study
* Participants will not be assigned any treatment intervention

The microdevice was developed as a tool with the ultimate goal to help screen several existing and investigational drugs directly within a patient's tumor to identify what drugs are the most effective for treating a patient's cancer.

Microdevices

Participant to receive standard of care therapy as previously determined by participant's treating oncologist and/or dermatologist, which may include a skin-directed or systemic therapy

Standard of care therapy

Participant to receive standard of care therapy as previously determined by participant's treating oncologist and/or dermatologist, which must include a systemic therapy.

Standard of care systemic therapy

Cecilia Larocca, MD

This research is being done to study the safety of implanting and retrieving a microdevice that releases up to 19 drugs directly within a cancerous lesion as a possible tool to evaluate the effectiveness of several approved cancer drugs against cutaneous T cell lymphoma and peripheral T cell lymphoma

This research study is a Pilot and Feasibility Study, which is the first time investigators are examining this study microdevice loaded with drugs in patients with cutaneous lesions of cutaneous T cell lymphoma (CTCL) or peripheral T cell lymphoma (PTCL) patients.

The FDA (the U.S. Food and Drug Administration) has not approved the use of all the drugs contained in the microdevice as a treatment for cutaneous or peripheral T cell lymphoma. All drugs used in this study are FDA approved. Some drugs are for different cancer indications. Romidepsin, vorinostat, bexarotene, brentuximab vedotin, pralatrexate, and mogamulizumab have been FDA approved for CTCL. The FDA has not approved the use of the microdevice as a tool to identify what cancer treatment is best for any disease.

In this research study, the investigators are investigating whether the microdevice loaded with 19 drugs can be safely inserted in and removed from cancerous skin lesion. The microdevice was developed as a tool with the ultimate goal to help screen several existing and investigational drugs directly within a patient's tumor to identify what drugs are the most effective for treating a patient's cancer.

This microdevice was investigated in laboratory studies and shown to help identify what drugs could be effective in treating a specific cancer type. The microdevice was able to release drugs only to the immediately surrounding tumor tissue in concentrations of one millionth of what is normally needed for a therapeutic dose. The microdevice can be retrieved along with a few millimeters of surrounding treated tumor tissue for analysis of tumor response to drug.

Expansion cohort may enroll only after initial cohort has completed enrollment

A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research

"Failure" will be considered any of the following:

1. Any grade 3 or 4 adverse events associated with device placement or retrieval
2. Any device resulting in "major" adverse events as listed below:

   * device unable to be found or unable to be retrieved
   * device invading into vessel or device embolism
   * infection or severe tissue damage or abnormal wound healing associated with device or procedure (as deemed by a neutral consultant e.g. dermatologist, ID specialist or surgeon)
   * severe allergic/hypersensitivity reaction
   * severe bleeding
3. Any device resulting in \*two or more\* "minor" adverse events as listed below:

   * device migration more than 10 mm
   * device fracture not causing a major adverse event
   * mild allergic/hypersensitivity reaction
   * manageable pain associated with biopsy procedure
   * minor bleeding For purposes of this endpoint, safety will be evaluated on a per-patient level, where an event is defined as any "failure" observed among all implanted devices.

For the feasibility endpoint, a "successful" procedure will be defined as the ability to retrieve the device (by either skin punch biopsy tool or surgical excision) without damaging tumor tissue surrounding the microdevice to allow for immunohistochemistry analysis.

For purposes of this endpoint, feasibility will be assessed on a per-device basis rather than a per-patient basis, with each device considered relatively independent in terms of placement, retrieval, and analysis.

Comparison of tumor responses to like drug delivered from separate microdevices.

Correlation of tumor response to drug released by microdevice compared with clinical response to systemic administration of like drug

Descriptive statistics will be used to summarize the quantitative measurements in cell number of different immunophenotypes and quantify signal transduction cascades. Descriptive statistics will be employed to summarize the variance in different measures of drug-induced microenvironment changes across participants.

Genetic alterations will be cataloged in terms of single nucleotide variants, insertions/deletions, and copy number changes and will be reported in a descriptive manner. Preliminary correlations between a specific genetic feature and specific clinical features will be tested using Fisher's exact test for categorical variables or the Wilcoxon Rank-Sum test for continuous variables. Analyses of correlations between genetic and clinical features in different specimen types and patient groups are exploratory, and will rely on descriptive statistics without formal hypothesis testing. For each genetic feature of interest (e.g. mutation, gene expression profile) we will divide patient samples into groups based on the presence or absence of the feature. We will then assess whether the presence of the feature is associated with clinical outcomes using odds ratios, or correlation between genetic feature and overall survival, using Kaplan Meier estimates, with 95% confidence intervals to each.

Dana-Farber Cancer Institute

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Penile Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Penile Diseases

Male Urogenital Diseases

Penile Cancer

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Pembrolizumab

Fluorouracil

Cisplatin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

-Pembrolizumab combined with standard of care therapy

* Standard of care therapy: ciplastin 70mg/m² IV D1(or carboplatin AUC 5) plus 5-Fluouracil 1000mg/m²/day IV( continuous infusion on Days 1-4) Q3W for 6 cycles

Patients will receive pembrolizumab at the dose of 200mg IV Q3W with maximum duration of 2 years (34 cycles-counting the part combined with chemotherapy)

Ciplastin 70mg/m² IV D1(or carboplatin AUC 5) plus 5-Fluouracil 1000mg/m²/day IV( continuous infusion on Days 1-4) Q3W for 6 cycles

Fernando Cotait Maluf

This is a phase II clinical trial evaluating activity, safety and patients reported outcomes of first-line pembrolizumab plus cisplatin (or carboplatin) plus 5-FU for patients with advanced penile squamous cell carcinoma.

The primary endpoint is overall responsa rate according to RECIST v1.1 at week 24.

Advanced penile squamous cell carcinoma is associated with dismal survival rates and a major impact on the quality of life. To date, unresectable or metastatic disease is managed by systemic therapy with platinum-based chemotherapy for patients with good performance status. The median PFS and OS on first-line platinum-based chemotherapy vary between 3-4 and 7-15 months, respectively. Chemotherapy induces objective responses in only 20-30% of penile cancer patients with rare complete responses and systemic treatment has not changed for decades. Therefore, this study's rationale is to explore the efficacy and safety of pembrolizumab combined with standard-of-care cisplatin(or carboplatin) plus 5-fluorouracil as part of the first-line therapy. Patients will receive pembrolizumab 200mg IV every three weeks with a maximum duration of 2 years (34 cycles-counting the combination with chemotherapy) in case of no progressive disease or intolerance. The investigators hypothesized that the combination of immunotherapy with standard cytotoxic chemotherapy may improve the overall response rate by RECIST v1.1 in this patient population.

Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer

A Phase II Trial of Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer

Proportion of patients with partial or complete response by investigator-assessed RECIST v1.1

Time from enrollment to progression by investigator-assessed RECIST 1.1 or death

Time from enrollment to death due to any cause.

Proportion of patients who have complete, partial response or stable disease by investigator-assessed RECIST v1.1

Comparison of initial and final scores of the European Organization for Research and Treatment (EORTC) C30 questionnaires.

Merck Sharp & Dohme LLC

Latin American Cooperative Oncology Group

Adenocarcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

Anti-Infective Agents

Immunomodulating Agents

Sunitinib

Interferons

Trovax

Placebo

subcutaneous low dose IL-2, interferon-α or sunitinib

The purpose of this study is to investigate whether TroVax, when added to first line standard of care therapy, improves survival for patients with locally advanced or metastatic clear cell renal adenocarcinoma.

This is an international, randomised, double blind, placebo controlled, parallel group study to investigate whether a minimum of three doses of TroVax® added to first-line standard of care therapy, prolongs the survival of patients with locally advanced or metastatic renal clear cell adenocarcinoma.

The primary endpoint is survival. The study is designed to be pragmatic, limiting additional study related investigations to a minimum. Protocol mandated scans and X-rays are limited to two time points (baseline and week 26) to permit comparison of the percentage of patients with progressive disease at 6 months as a secondary efficacy endpoint. Six months was selected based on review of published literature indicating that progressive disease was commonly observed by 26 weeks in patients with renal cancer. Endpoints such as tumour response by RECIST are considered of secondary importance to survival and will be determined by radiological examinations ordered at the discretion of the investigator based on the clinical status of the patient and will be based the interpretation of the patient's care-team (investigator and local radiologist).

After signing the study informed consent form and meeting the baseline enrolment criteria patients will be assigned by the investigator (their physician) to one of the following defined first-line standard of care regimens based on what is best for the patient and consistent with local practice:

1. subcutaneous low dose IL-2
2. interferon-α (excluding pegylated IFNα)
3. sunitinib

TroVax® is administered at a dose of 1E9TCID50/ml in 1ml by injection into the deltoid muscle of the upper arm at regular intervals up to 8 weeks apart up to a maximum of 13 doses.

TroVax Renal Immunotherapy Survival Trial

Randomised,Double-blind,Placebo-controlled,Parallel Group Study TroVax, Added to First-line Standard of Care, Prolongs Survival of Patients With Locally Advanced or Metastatic Clear Cell Renal Adenocarcinoma.

Sanofi

Oxford BioMedica

Nutritional and Metabolic Diseases

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Proteostasis Deficiencies

Metabolic Diseases

Neoplasms, Plasma Cell

Paraproteinemias

AL Amyloidosis

Doxycycline

Bortezomib

Anti-Bacterial Agents

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Systemic amyloidoses are rare diseases affecting approximately 1 in 100,000 persons each year.

In systemic amyloidoses abnormal proteins deposit in bodily organs and severely impair their function, causing death if not treated effectively. Light chain (AL) amyloidosis is caused by a usually small population of plasma cells (the cells that produce antibodies). These cells produce part of antibodies, the light chains (LC) that form amyloid deposits. Almost every organ, with the exception of the brain, can be affected by AL amyloidosis. The heart is involved in three fourths of patients and is responsible for almost all the deaths occurring in the first 6 months after diagnosis. Current therapy of AL amyloidosis is based on drugs targeting the plasma cells producing the amyloid-forming LC. At present, most patients receive a powerful anti-plasma cell drug, bortezomib, as part of their initial treatment. However, bortezomib-based therapy, can improve heart involvement only in less than one third of patients with AL amyloidosis, and many patients (approximately one third) still die within 12 months from diagnosis. Early cardiac deaths remain an acute unmet need and the major determinant of overall outcome in this disease. Thus, there is the need of alternative means to treat heart involvement in AL amyloidosis. Doxycycline is a widely used, well tolerated, antibiotic that has been marketed for decades and used to treat a number of different infectious diseases caused by bacteria. This molecule has been extensively studied in the laboratory, in animal models and, more recently, in small studies involving patients, for its potential of improving cardiac damage in amyloidosis. These studies showed that doxycycline disrupts amyloid deposits, reduces the amyloid load in a mouse model, and counteracts the toxicity exerted by amyloid-forming LCs on C. elegans, a worm whose pharynx is used as a model resembling human heart. In a small clinical study, doxycycline was given to patients with cardiac AL amyloidosis during treatment for their underlying plasma cell disease. This resulted in a remarkable improvement of survival compared to "matched historical controls" (i.e. similar patients who had received only anti-plasma cell therapy without doxycycline in the past). Based on these promising preliminary results, we designed the present clinical trial to assess whether the addition of doxycycline to anti-plasma cell therapy can improve survival in patients with cardiac AL amyloidosis who were not previously treated. The rate of survival at 12 months will be compared in patients receiving doxycycline and in controls receiving standard antibiotic therapy, together with anti-plasma cell therapy. Patients will be assessed for parameters of plasma cell disease, heart involvement and possible involvement of other organs, as well as for quality of life. To make sure that patients who will receive doxycycline and those who will not have comparable severity of cardiac disease, patients will be stratified according to the stage of cardiac involvement. Patients with very advanced heart dysfunction will not be enrolled in the trial, because preliminary data indicate that doxycycline is of little or no benefit in these subjects. Patients will be randomized to receive doxycycline or standard antibiotics in combination with anti-plasma cell therapy. Bortezomib-based treatment directed against plasma cells will be delivered according to each participating institutions' guidelines. Doxycycline will be administered at a dosage of 100 mg two times a day, which is usual in the treatment of bacterial diseases. Standard antibiotics will be delivered according to each participating institutions' guidelines (provided that drugs of the same class as doxycycline are not administered) in the control arm. Patients will be provided a diary to record possible adverse events and will be instructed accordingly. Patients will be evaluated at trial centers every 2 months for treatment efficacy and toxicity. In case of unsatisfactory response second-line therapy will be initiated. In the absence of unacceptable toxicity, doxycycline administration will be continued for the entire duration of follow-up (12 months).

This will be an open-label parallel-group randomized (1:1) trial. Control patients receive standard supportive therapy.

A Trial of Doxycycline vs. Standard Supportive Therapy in Newly-diagnosed Cardiac AL Amyloidosis Patients Undergoing Bortezomib-based Therapy

A Randomized Phase II/III Trial of Doxycycline vs. Standard Supportive Therapy in Newly-diagnosed Cardiac AL Amyloidosis Patients Undergoing Bortezomib-based Therapy

IRCCS Policlinico S. Matteo

Professor

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Durvalumab

Part 1 of this trial will use a traditional 3+3 design will be used for this trial (i.e. cohort sizes of 3 patients for the first and second cohort at each dose level). Dose escalation will occur as long as there are minimal dose limiting toxicities.The expectation is that 9 patients will be enrolled to the trial during part 1.This is based on the expectation that all dose levels are safe (i.e. patients will not experience DLTs at all dose levels). The range of patients needed will be 6-12 patients.

Part 2 of this trial will be an expansion cohort. A total of 8 additional patients will be enrolled at the dose level determined to be the MTD in part 1 of the study. These 8 patients will be used to confirm that the MTD is a safe combination, as well as provide additional patients to investigate the efficacy for the treatment combination.

Note: Standard of care surgery will follow 3-6 weeks after medication and radiation treatment.

Patients will receive one dose of neoadjuvant durvalumab 1500 mg approximately 3-6 weeks prior to standard of care surgery. It will be given concurrently with the first dose of radiation (RT). Patients will receive up to six doses of durvalumab and radiation post-operatively.

The starting RT dose level will be given as 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease only to minimize exposure to normal tissue. If toxicity develops and surgery is delayed by more than 8 weeks (qualifying as a DLT), the radiation dose will be dropped per protocol for the next set of patients. If this dose is tolerated, the dose will be increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients.

Stereotactic Body Radiation Therapy (SBRT)

Patients will proceed to surgical resection 3-6 weeks after radiation as recommended by the ENT surgeon.

Standard of Care Therapy

Sana Karam, MD, PhD

This is a multi-center, prospective, single-arm phase I/Ib safety trial. Patients eligible for treatment must be diagnosed with non-metastatic, biopsy-proven stage II-IVB oral cavity, stage III-IVB larynx and hypopharynx, or stage III-IVB HPV/p16 negative intermediate-high risk oropharynx head and neck cancer, and must be eligible and amenable to surgical resection.

This study will be enrolled using a 3+3 model. Patients will receive one dose of neoadjuvant durvalumab 1500 mg approximately 3-6 weeks prior to standard of care surgery. It will be given concurrently with the first dose of radiation (RT). The starting RT dose level will be given as 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease (Table 1) only to minimize exposure to normal tissue. If toxicity develops and surgery is delayed by more than 8 weeks (qualifying as a DLT), the radiation dose will be dropped per protocol for the next set of patients. If this dose is tolerated, the dose will be increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients. Patients will proceed to surgical resection approximately 3-6 weeks after radiation as recommended by the ENT surgeon.

Radiotherapy With Durvalumab Prior to Surgical Resection for HPV Negative Squamous Cell Carcinoma

Phase I/Ib Trial of Radiotherapy in Combination With Durvalumab (MEDI4736) Prior to Surgical Resection for HPV Negative Squamous Cell Carcinoma of the Head and Neck (HNSCC)

The Maximum Tolerated Dose (MTD) and Dose Limiting Toxicities (DLT) will be discovered by using the 3+3 study design.

Tumor response to neoadjuvant therapy (durvalumab + SBRT) will be assessed by pathology review of the surgical specimen. Response will be labeled as complete pathologic remission, microscopic residual tumor (only scattered foci of residual tumor cells) or macroscopic residual tumor.

Overall survival (OS), along with locoregional control and distant control will be determined from the time of enrollment to date of death due to any cause. OS will be evaluated by Kaplan-Meier estimate.

Analysis of gene expression of RNA levels and entire genome sequences using the 10X Genomics single-cell RNA-sequencing platform.

Phenotypic analysis of T cells and assessment of intracellular and circulating cytokines using multiplex mass flow cytometry to analyze phenotypic changes, functional response of cytokine production, and activation status of tumor infiltrating lymphocytes (TILs), circulating T cells (especially CD8 and PD-1 expression), and peripheral blood mononuclear cells (PBMCs).

Examination of intratumoral immune cell infiltration using the Perkin Elmer Vectra 3 and tissue microarrays.

Grading of adverse effects (AEs) will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Short- and long-term quality of life will be obtained using FACT H\&N v4 and will be assessed at baseline, with each cycle, post-SBRT, post-surgically, and throughout adjuvant therapy on a standard schedule.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma	NCT04045470	Cutaneous T Cel... Peripheral T Ce...	Microdevices Standard of car... Standard of car...	18 Years -	Dana-Farber Cancer Institute
Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer	NCT04224740	Penile Carcinom...	Pembrolizumab Standard of car...	18 Years -	Latin American Cooperative Oncology Group
TroVax Renal Immunotherapy Survival Trial	NCT00397345	Clear Cell Rena...	Trovax Placebo Standard of car...	18 Years -	Oxford BioMedica
A Trial of Doxycycline vs. Standard Supportive Therapy in Newly-diagnosed Cardiac AL Amyloidosis Patients Undergoing Bortezomib-based Therapy	NCT03474458	Cardiac AL Amyl...	Doxycycline Standard of car...	18 Years -	IRCCS Policlinico S. Matteo
Radiotherapy With Durvalumab Prior to Surgical Resection for HPV Negative Squamous Cell Carcinoma	NCT03635164	Squamous Cell C...	Durvalumab Stereotactic Bo... Standard of Car...	18 Years -	University of Colorado, Denver
A Trial of Doxycycline vs. Standard Supportive Therapy in Newly-diagnosed Cardiac AL Amyloidosis Patients Undergoing Bortezomib-based Therapy	NCT03474458	Cardiac AL Amyl...	Doxycycline Standard of car...	18 Years -	IRCCS Policlinico S. Matteo
Radiotherapy With Durvalumab Prior to Surgical Resection for HPV Negative Squamous Cell Carcinoma	NCT03635164	Squamous Cell C...	Durvalumab Stereotactic Bo... Standard of Car...	18 Years -	University of Colorado, Denver
Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer	NCT04224740	Penile Carcinom...	Pembrolizumab Standard of car...	18 Years -	Latin American Cooperative Oncology Group

Spots Global Cancer Trial Database for standard of care therapy