Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Cholangiocarcinoma

Carcinoma, Hepatocellular

Biliary Tract Neoplasms

Liver Neoplasms

Bile Duct Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Bile Duct Diseases

Biliary Tract Diseases

Bile Duct Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Chlorotrianisene

Tremelimumab

Antineoplastic Agents, Immunological

Flat dose of 75 mg every 4 weeks for up to 4 doses.

TACE will be performed on Day 36 (+/-96hrs).

Trans-arterial Catheter Chemoembolization (TACE)

RFA will be performed on Day 36 (+/-96hrs).

Radiofrequency Ablation (RFA)

Cryoablation will be performed on Day 36 (+/-96hrs).

Cryoablation

Tim F Greten, M.D.

BACKGROUND:

* Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. The term ablative therapies applies to trans-arterial catheter chemoembolization (TACE), radiofrequency ablation (RFA) and cryoablation (CA).
* The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE, CA and RFA in patients with advanced hepatocellular carcinoma (HCC) and biliary tract carcinomas (BTC). We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy.
* Based on the concept of programmed death-ligand 1 (PDL1)-mediated adaptive resistance and the emerging role of programmed cell death protein 1 (PD1) therapy in HCC, we would like to evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in HCC and BTC.

Objectives:

- To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (either alone or with cryoablation, TACE or RFA) and in patients with advanced biliary tract carcinoma (BTC) (either alone or with cryoablation or RFA).

ELIGIBILITY:

* Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma).
* Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply.
* Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.

DESIGN:

We will evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in cohorts A (HCC; N=40) and B (BTC; N=30). The first N=10 patients in both cohorts will receive tremelimumab and durvalumab only (i.e. No interventional radiologic procedures).

* A: Advanced HCC, BCLC# Stage B/C

  * N= 1st 10 pts: No ablative procedure Cryoablation/RFA/TACE##
  * Tremelimumab 75mg flat dose every (q)28 days for 4 doses; Durvalumab 1500mg flat dose q28 days until end of study (EOS)###
  * 40 total: 10 trem+ dur alone; 10 trem+ dur + TACE; 10 trem + dur + RFA; 10 trem + dur + cryo
* B: Intra/extra-hepatic cholangiocarcinoma

  * N= 1st 10 patients (pts): No ablative procedure; RFA/ cryoablation
  * Tremelimumab 75mg flat dose q28 days for 4 doses; Durvalumab 1500mg flat dose q28 days until EOS###
  * 30 total: 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem

    * BCLC = Barcelona clinic liver cancer staging system

      * For BCLC stage B patients TACE may be repeated as per standard of care

        * EOS = End of study treatment or meeting any of the off-treatment or off study criteria.

BACKGROUND:

* Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. The term ablative therapies applies to trans-arterial catheter chemoembolization (TACE), radiofrequency ablation (RFA) and cryoablation (CA).
* The underlying hypothesis of this study is that the effect of immune checkpoint inhibition can be enhanced by TACE, CA and RFA in patients with advanced hepatocellular carcinoma (HCC) and biliary tract carcinomas (BTC). We have already demonstrated proof of principle as well as safety and feasibility of this approach with anti-CTLA4 therapy.
* Based on the concept of PDL1-mediated adaptive resistance and the emerging role of PD1 therapy in HCC, we would like to evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in HCC and BTC.

Objectives:

- To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (either alone or with cryoablation, TACE or RFA) and in patients with advanced biliary tract carcinoma (BTC) (either alone or with cryoablation or RFA).

ELIGIBILITY:

* Histologically or cytologically confirmed diagnosis of HCC or biliary tract carcinoma OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma).
* Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply.
* Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.

DESIGN:

We will evaluate the combination of tremelimumab and durvalumab (with ablative therapies) in cohorts A1 (HCC; Barcelona clinic liver cancer staging system (BCLC) stage C; N=10), A2 (HCC; BCLC stages B/C; N=30) and B (BTC; N=30). The patients in cohort A1 and first 10 patients in cohort B will receive tremelimumab and durvalumab only (i.e. no interventional radiologic procedures).

A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC)

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

In addition, all large scale genomic sequencing data will be shared with subscribers to database of Genotypes and Phenotypes (dbGaP).

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

PFS is the median amount of time subject survives without disease progression 6 months after treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE)v4.0. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.

National Cancer Institute (NCI)

Principal Investigator

RFA/TACE Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study.

30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation

Radiofrequency Ablation/Trans-arterial Catheter Chemoembolization (RFA/TACE)

Tremelimumab (trem) 75mg flat dose every (q)28 days for 4 doses and Durvalumab (dur) 1500mg flat dose q28 days until end of study.

30 total (e.g. Per the study design, this is the number of participants we planned to treat): 10 trem+ dur alone; 10 trem + dur + RFA; 10 trem + dur + cryoablation

Radiofrequency Ablation/Cryoablation (RFA/CA)

Enrolled But Not Treated

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Tim F. Greten

6 Month Progression Free Survival (PFS)

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Number of Grades 1-5 Adverse Events Related to Tremelimumab and Durvalumab

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

Overall Study

Biliary Tract Cancer

Hematinics

Immunomodulating Agents

Liver Extracts

Escalating doses of Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)

Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)

Tremelimumab + Transarterial Catheter Chemoembolization (TACE)

Tremelimumab + Radiofrequency Ablation (RFA)

3.5 mg/kg or 10 mg /kg intravenous (IV) every 4 weeks times 6 doses and then every 12 weeks for 2 years

Performed on Day 36 and may be repeated (as per standard of care) on months 3, 7, and 13, and every (q)6 months thereafter (if indicated)

TACE

Background:

- Tremelimumab is a cancer treatment drug that helps the immune system recognize and destroy cancer cells. Researchers want to see if it can be used to treat advanced liver cancer. The drug will be given with one of two types of treatment for liver cancer. The first type, transarterial catheter chemoembolization (TACE), injects chemotherapy drugs into the tumor through the main blood vessel that is feeding it. That blood vessel is then closed off to help keep the drugs in the tumor longer. The second type, radiofrequency ablation (RFA), uses a heated probe to destroy the tumor tissue. Researchers want to study how safe and effective these treatments are with the study drug.

Objectives:

- To test the safety and effectiveness of Tremelimumab with TACE or RFA for advanced liver cancer.

Eligibility:

- Individuals at least 18 years of age who have advanced liver cancer that has not responded to other treatments.

Background:

Worldwide, hepatocellular carcinoma (HCC) is the fifth most common malignancy with a median survival of 6-9 months. For patients with advanced disease sorafenib is the only approved drug and this has limited benefit.

Tremelimumab is a monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Anti-CTLA4 therapy has been shown to enhance anti-tumor immunity by blocking tumor-induced immune suppression of cytotoxic T cells.

Various tumor ablative procedures and techniques have been shown to result in immunogenic cell death and induction of a peripheral immune response. Both transarterial catheter chemoembolization (TACE) and radiofrequency ablation (RFA) have been shown to do this, as well as cryoablation and external beam radiation.

The underlying hypothesis of this study is that the effect of anti-CTLA4 treatment can be enhanced by TACE or RFA in patients with advanced hepatocellular carcinoma. We will also evaluate this in the context of cryoablation and radiation in hepatocellular carcinoma (HCC) and RFA in cholangiocarcinoma.

Objective:

To assess the safety and feasibility of combining Tremelimumab with trans-arterial catheter chemoembolization (TACE) radiofrequency ablation (RFA), or cryoablation in patients with advanced HCC.

Eligibility:

Histologically or cytologically confirmed diagnosis of HCC.

Childs-Pugh A/B7 cirrhosis only is allowed. If patient does not have cirrhosis, this limitation does not apply.

Barcelona Clinic Liver Cancer (BCLC) Stage B and C patients.

Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.

Tremelimumab With Chemoembolization or Ablation for Liver Cancer

A Pilot Study of Tremelimumab - A Monoclonal Antibody Against CTLA-4 in Combination With Trans-Arterial Catheter Chemoembolization (TACE), Radiofrequency Ablation (RFA), or Cryoablation in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC)

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Best response was assessed by the combined Response Evaluation Criteria in Solid Tumors (RECIST and the Modified Immune-Related Response Criteria (irRC). Complete Response (CR) is disappearance of all target lesions. Any patjhological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if it is the smallest on study). The appearance of one or more lesions is also considered progressions.

Progression free survival is defined as the amount of time a subject survives without disease progression after treatment. Progression is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if it is the smallest on study). The appearance of one or more lesions is also considered progressions.

Overall survival is defined as the amount of time a subject survives after therapy.

All deaths in the mortality module are attributable to progressive disease (all deaths that occurred are reported).

Escalating doses of Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)

Tremelimumab: 3.5 mg/kg intravenous (IV) every 4 weeks times 6 doses and then every 12 weeks for 2 years

RFA: Performed on Day 36

TACE: Performed on Day 36 and may be repeated (as per standard of care) on months 3, 7, and 13, and every (q)6 months thereafter (if indicated)

Pilot 1/Arm A1-Tremelimumab + RFA or TACE

Tremelimumab + Radiofrequency Ablation (RFA) or Transarterial Catheter Chemoembolization (TACE)

Tremelimumab: 10 mg /kg intravenous (IV) every 4 weeks times 6 doses and then every 12 weeks for 2 years

RFA: Performed on Day 36

TACE: Performed on Day 36 and may be repeated (as per standard of care) on months 3, 7, and 13, and every (q)6 months thereafter (if indicated)

2/Arm A2 -Tremelimumab + RFA or TACE

Tremelimumab + Transarterial Catheter Chemoembolization (TACE)

Tremelimumab: 10 mg /kg intravenous (IV) every 4 weeks times 6 doses and then every 12 weeks for 2 years

TACE: Performed on Day 36 and may be repeated (as per standard of care) on months 3, 7, and 13, and every (q)6 months thereafter (if indicated)

3/Arm B - Tremelimumab + TACE

Tremelimumab + Cryoablation

Tremelimumab: 10 mg /kg intravenous (IV) every 4 weeks times 6 doses and then every 12 weeks for 2 years

Cryoablation: Performed on Day 36

5/Arm D - Tremelimumab + Cryoablation

Tremelimumab + Radiofrequency Ablation (RFA)

Tremelimumab: 10 mg /kg intravenous (IV) every 4 weeks times 6 doses and then every 12 weeks for 2 years

RFA: Performed on Day 36

6/Arm E - Tremelimumab + RFA

2/Arm A2 - Tremelimumab + RFA or TACE

Any surgical resection

Any TACE

Any chemotherapy

Any radiation therapy

Misc. therapy - Y90

Misc. therapy - Hyperthermia

Transarterial catheter chemoembolization (TACE)

Previous Therapy

Number of Participants With Serious and Non-Serious Adverse Events Regardless of Attribution

Complete Response

Partial Response

Stable Disease

Progressive Disease

Not Evaluable

Tremelimumab + Radiofrequency Ablation (RFA)

Tremelimumab:10 mg /kg intravenous (IV) every 4 weeks times 6 doses and then every 12 weeks for 2 years

RFA: Performed on Day 36

Number of Participants With Best Response

Progression Free Survival (PFS)

Overall Survival

Symptoms and General Pathology

Infections

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Warts

Condylomata Acuminata

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Genital Diseases

Urogenital Diseases

Anti-Infective Agents

Imiquimod

Immunologic Factors

Adjuvants, Immunologic

Interferons

Imiquimod 5% cream three times per week for 4 weeks (1 sachet)

1 or 2 sachet(s)

vehicle cream three times per week for 4 weeks (1 sachet)

1 or 2 sachet(s)

vehicle cream

Fausto Boselli, MD

The purpose of this study is to compare the recurrence rate following total clearance of external genital warts (EGWs) when clearance has been obtained by imiquimod (3 applications per week for 4 weeks) followed by ablative therapy (laser or electrocautery therapy) with that from just ablative therapy treatment alone.

To compare the recurrence rate 24 weeks after ablative therapy in subjects with external genital warts trated with imiquimod, 3 applications per week for 4 weeks followed by ablative therapy versus vehicle, 3 applications per week for 4 weeks followed by ablative therapy. A recurrence is defined as the investoigator-assessed occurrence of lesion(s) within the baseline area cleared by the treatment: imiquimod/vehicle then ablative therapy (either the initial ablative therápy session (A0), or if required for complete clearance of baseline lesions, a second ablative therapy session (A2).

Study of Imiquimod Cream Prior to Ablative Therapy in External Ano-Genital Warts

Multicenter, Randomised, Double-blind, Vehicle-controlled Study Comparing Recurrence Rate Following Imiquimod 5% Cream or Vehicle 3 Times Per Week for 4 Weeks Prior to Ablative Therapy in Subjects Suffering From External Ano-Genital Warts

MEDA Pharma GmbH & Co. KG

Joachim Maus, MD, Director Clinical Development

Immune System Diseases

Carcinoma, Squamous Cell

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

HIV Seropositivity

Anus Neoplasms

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Anus Diseases

Rectal Diseases

Anal Cancer

Vaccines

Ablative therapy involving electrocautery (EC) will occur for participants with AIN-2 and AIN-3. The Hyfrecator ® 2000 Electrosurgical System will be used for EC therapy.

The control arm includes active surveillance with observation alone; no treatment in AIN-2 and -3.

Lesion is ablated by the The Hyfrecator ® 2000 Electrosurgical System. During electrocautery (EC) with The Hyfrecator, a gentle brushing technique occurs and the tissue is removed with forceps.

The Hyfrecator ® 2000 Electrosurgical System

No treatment to AIN-2 or AIN-3, only active surveillance.

Observation Alone

Irving Salit, MD

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide. Infection by certain high-risk oncogenic types of HPV (HR-HPV) is the major cause of several cancers in men, notably squamous cell carcinoma (SCC) of the anal canal. Rates of anal infection with these HR-HPV strains and the resultant high-grade anal dysplasia and anal cancer are much higher in men who have sex with men (MSM) than in the general population. Co-infection with human immunodeficiency virus (HIV) further amplifies this burden, making the rates of anal SCC in HIV-positive MSM higher than the historic rates of cervical cancer prior to the adoption of routine cervical cytology screening. Despite these alarming statistics, there are no established protocols for optimal screening and treatment of anal HPV and cancer precursors, nor has there been any widespread rollout of organized screening programs anywhere in Canada. Further, not only does HPV directly cause significant disease in these men, but there is growing epidemiologic evidence that HPV infection may enhance sexual transmission of HIV. These significant knowledge gaps translate into fundamental deficiencies in care for HIV-positive MSM.

The HPV Screening and Vaccine Evaluation in MSM (HPV-SAVE) study team will recruit a large group of MSM from various Ontario and Vancouver clinics, in order to carry out a number of different studies. The HPV-SAVE team brings together community and internationally-recognized experts in HPV and HIV disease and mucosal immunology, to better define the optimal approaches for primary and secondary prevention and treatment of HPV-associated anal disease among HIV-positive MSM, and to explore biological mechanistic evidence regarding the potential role of HPV as a co-factor for HIV transmission. This will yield critical information which can lead to improvement in the health of MSM, and will provide a foundation on which to build further, large-scale screening and treatment trials on a national level. The primary aim of the current study is to systematically compare ablative therapy versus intensive observation alone (also known as 'watchful waiting') in outcomes relating to high-grade anal dysplasia.

Since the 1990s, combination antiretroviral therapy (cART) has markedly reduced HIV-related opportunistic infections and mortality \[1\], and increased the life expectancy of people living with HIV \[2\]. While acquired immune deficiency syndrome (AIDS)-defining malignancies have declined \[3,4\], non-AIDS defining malignancies continue to occur at higher rates in HIV-infected persons than in the general population \[4\]. Amongst these are cancers associated with HPV which is responsible for the vast majority of cervical cancers (itself a well-established AIDS-defining illness), and an estimated 90% of SCC of the anal canal \[5\]. cART not only fails to protect against anal pre-cancers and cancers \[4,6,7\], but the incidence of anal SCC is increasing in the cART era \[6,8\]. Because of this increasing burden of disease, there is an urgent need to find effective ways of preventing anal SCC in those living with HIV. This includes screening for anal cancer precursors and ablative treatment of these lesions.

Though it is infrequent at a rate of 1 per 100 000, anal SCC is on the rise in the general population \[9\]. It occurs at significantly higher rates in HIV-positive men - particularly among men who have sex with men (MSM) - with an estimated rate of 60 to 160 per 100 000 \[4\], and no evidence of slowing in the era of increased cART use \[10\] (See Figure 1). In fact, rates of anal cancer among HIV-infected MSM are comparable to rates of cervical cancer in women prior to the adoption of routine screening for cervical dysplasia \[11\]. According to data from the Public Health Agency of Canada, rates of cervical cancer in 1972 were 18 per 100 000, dropping to just under 8 per 100 000 in 2004 \[12\]. In addition to its etiologic association with HPV, anal cancer shares many similarities with cervical cancer. Both are squamous cell cancers occurring at the squamocolumnar junction \[13,14\] and both likely arise from histologically-similar dysplastic precursor lesions \[15,16\]. It is postulated that a critical step in anal cancer carcinogenesis is the establishment of persistent infection with oncogenic HPV in the anal canal \[16\]. Though the majority of HPV infections are considered transient and will eventually clear even in HIV-positive individuals \[17\], HIV-positive individuals have higher rates of persistent infection, especially with oncogenic HPV types \[18\].

Of the greater than 170 HPV types, over 50 favour the anogenital area and, on the basis of epidemiologic and phylogenetic data, these have been classified by the International Agency for Research on Cancer \[19\]. The vast majority of anal cancers (as well as cervical cancers) are caused by two high-risk HPV types: HPV type 16 and HPV type 18 which are responsible for 66% and 5% of anal cancers, respectively \[20\]. HPV lesions caused by low-risk HPV (LR-HPV) types include condylomata (commonly known as 'genital warts'), of which 90% are caused by HPV types 6 and 11 \[21\]. Prevention strategies for anal cancers have emerged that are analogous to strategies used in cervical cancer screening, in that the aim is to identify precursor lesions which can then be removed before progression to cancer. Screening and detection rely on a combination of anal cytology (Papanicolaou, or Pap smear), anal HPV detection and high-resolution anoscopy (HRA) which is analogous to colposcopy). Visually-directed anal biopsy during HRA is considered the gold standard for detecting dysplastic lesions such as high-grade anal intraepithelial neoplasia (HGAIN; typically graded as AIN-2 or -3) \[16,22\]. Anal cytology is generally used as a screening test to determine whether HRA is needed; however, cytology is an imperfect predictor of intra-anal HGAIN. Despite the clear evidence indicating the benefit of screening and treatment procedures in cervical cancer screening, no large rigorous studies have been performed to assess such strategies in anal cancer prevention in men or women.

The HPV-SAVE Study Team: HPV Screening and Vaccine Evaluation in Men Who Have Sex With Men

A Randomized Controlled, Open-label Trial Examining the Efficacy, Safety, and Tolerability of Ablative Therapies for High-grade Anal Dysplasia Versus Observation Alone in HIV-positive Men Who Have Sex With Men (MSM)

Histologic resolution of high-grade AIN after treatment completion, with ablative therapies or surveillance alone. Resolution of high-grade AIN will be defined as histologic diagnosis of AIN-1 or normal at the post treatment HRA.

Resolution of high-grade AIN after treatment on a per-lesion basis. Histologic resolution of high-grade AIN after treatment completion, with ablative therapies or surveillance alone. Resolution of high-grade AIN will be defined as histologic diagnosis of AIN-1 or normal at the post treatment HRA.

Recurrence rates of high-grade AIN following ablative therapy on a per lesion basis.

Number of participants assessed on safety, tolerability and acceptability of the different intervention arms and the different treatments in the ablative therapies arms. Evaluation of adverse events and questionnaire-assessed acceptability by intervention arms and ablative treatment type.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC)	NCT02821754	Biliary Tract N... Liver Cancer Hepatocellular ... Cholangiocarcin... Bile Duct Cance...	Durvalumab Tremelimumab Trans-arterial ... Radiofrequency ... Cryoablation	18 Years -	National Institutes of Health Clinical Center (CC)
Tremelimumab With Chemoembolization or Ablation for Liver Cancer	NCT01853618	Heptocellular C... Biliary Tract N... Liver Cancer Hepatocellular ... Biliary Cancer	Tremelimumab RFA TACE Cryoablation	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Study of Imiquimod Cream Prior to Ablative Therapy in External Ano-Genital Warts	NCT00189293	Genital Warts	Imiquimod vehicle cream	18 Years -	Viatris Inc.
The HPV-SAVE Study Team: HPV Screening and Vaccine Evaluation in Men Who Have Sex With Men	NCT02503111	Anal Dysplasia Human Papilloma... Anal Cancer	The Hyfrecator ... Observation Alo...	18 Years -	University Health Network, Toronto
Study of Imiquimod Cream Prior to Ablative Therapy in External Ano-Genital Warts	NCT00189293	Genital Warts	Imiquimod vehicle cream	18 Years -	Viatris Inc.

Spots Global Cancer Trial Database for ablative therapy