Neoplasms

All Conditions

Infections

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Virus Diseases

Papilloma

Neoplastic Cells, Circulating

Anus Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Neoplasm Metastasis

Neoplastic Processes

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Anal Cancer

Patients with newly diagnosed anal cancer who by standard of care are eligible for induction chemotherapy prior to definitive CRT or radiotherapy alone (RT) will be screened according to inclusion- and exclusion criteria. Patients eligible for induction chemotherapy will be patients with locally advanced or synchronous metastatic anal cancer.

Karen L Wind, MD

Eva Serup-Hansen, PhD

Birgitte M Havelund, PhD

To investigate the prognostic and predictive value of plasma HPV (pHPV) prior, during and after induction chemotherapy (ICT) in locally advanced squamous cell carcinoma of the anus (SCCA) or synchronous metastatic SCCA patients treated with ICT prior to definitive (chemo)radiotherapy ((C)RT) according to multidisciplinary team (MDT) conferences based decisions. Further to investigate the use of pHPV measurements and other relevant markers for prediction of response and survival after ICT prior to definitive (C)RT.

Anal cancer is a rare malignancy with approximately 200 new cases in Denmark per year, and the standard treatment is chemoradiotherapy (CRT). The treatment is centralised at three oncological departments at Aarhus University Hospital, Herlev Hospital and Vejle Hospital. The majority of anal cancers are squamous cell carcinomas (SCCA) and are strongly associated with human papilloma virus (HPV) which can be detected in tumour tissue in more than 80% of cases. Patients with large tumours, tumours invading nearby organs and/or local lymph node metastases could be treated with induction chemotherapy (ICT) in cases where downsizing prior definitive treatment is needed. Selected patients with metastatic (M1) SCCA could also be treated with ICT with the purpose of making definitive treatment possible.

HPV, cell-free DNA, circulating tumour DNA and immune related markers:

HPV is a virus group consisting of more than 130 subtypes, of which a minor part is categorised as oncogenic types. The most common HPV subtypes found in SCCA is HPV-16 and -18, but the total landscape of HPV subtype distribution in SCCA is sparsely investigated. Small fragments of cell-free DNA (cfDNA) can be detected in the circulation with elevated levels in cancer patients, but also in other circumstances. Aberrant methylation of DNA occurs in almost all malignant tumours and is shed into the circulation. The level of tumour specific methylated DNA (meth-ctDNA) can be analysed by modern PCR technology. It seems to hold biological information, which holds promise of clinical utility. The literature has focused on colorectal cancer and meth-ctDNA has been introduced as a prognostic marker. The possible importance in anal cancer has not been elucidated which is one the aims of the present protocol. With a simple blood test (so called "liquid biopsy"), it is possibility to characterise both the level of total cfDNA and meth-ctDNA. HPV associated anal cancer has a viral sequence integrated into the genome of the cancer cells. In HPV associated anal cancer meth-ctDNA is shredded to the blood stream, and can be measured as HPV tumour cell DNA (plasma HPV or pHPV). The observational and translation part of the DACG Plan-A study have shown that levels of pre-treatment pHPV are higher in large tumours compared to small and higher in node positive disease compared to node negative which is in agreement with results on advanced anal cancer where pHPV levels were correlated to tumour burden. The Plan-A study have also shown that pHPV is eliminated during CRT in case of response to treatment.

Immunotherapy has changed the treatment of several malignant tumours, especially malignant melanoma. The checkpoint inhibitors block PD/PD-L1 interaction, which elicits immune response to the malignant tumour. The treatment also seems to have effect in anal cancer. The literature is sparse, but a number of studies are ongoing. It is therefore well motivated to analyse one of the central stakeholders in the immune response. The level of PD-L1 in serum holds potential as a prognostic marker in anal cancer.

Perspective:

In patients treated with ICT prior to definitive CRT it is crucial not to exceed the necessary amount of potentially toxic treatment cycles and the ability of pHPV to address early response or progression is highly relevant. Complete response after ICT have been reported and treatment with ICT consisting of e.g. cisplatin, 5-flourouracil, leuroverin and ifosfamide (CILF) have shown a complete local tumour response rate of 15% and prediction of response is therefore highly relevant. In the metastatic setting taxol and carboplatin has now been introduced as first line option. This combination is also a relevant candidate for ICT. The potential perspective will be development of studies with pHPV guided intensified ICT.

Purpose:

To investigate the prognostic and predictive value of pHPV prior, during and after ICT in patients treated with ICT according to multidisciplinary team (MDT) conferences based decisions. Further to investigate the use of pHPV measurements and other relevant markers for prediction of response and survival after ICT prior to definitive CRT.

Circulating Biomarkers in Patients With Anal Cancer Treated With Induction Chemotherapy

Overall survival: Time from diagnosis to time of dead or date of last follow-up.

Time from end of treatment to progression, recurrence or death whatever comes first.

Time from end of treatment to recurrence (locoregional or distant failure) or death whatever comes first.

Overall survival: Time from diagnosis to time of death or date of last follow-up.

Aarhus University Hospital

Medical Doctor, principal investigator

Skin and Connective Tissue Diseases

Skin Neoplasms

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Cemiplimab

Antineoplastic Agents, Immunological

Participants have locally advanced, unresectable cutaneous squamous cell carcinoma/CSCC

Participants will undergo baseline imaging, followed by two doses of neoadjuvant cemiplimab at a dose of 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days). Then, participants will receive concurrent cemiplimab 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days) concurrently with RT to 70 Gy in 35 fractions over 7 weeks. Thereafter, participants will receive 38 weeks of cemiplimab 350 mg intravenously over 30 minutes every 3 weeks (+/-3 days) for a cumulative total of 12 months of cemiplimab.

Participants will receive radiotherapy to 70 Gy in 35 fractions over 7 weeks concurrently with cemiplimab

Radiotherapy

Christopher Barker, MD

Lara Dunn, MD

Ryan Lanning, MD, PhD

Evan Wuthrick, MD

Zachary Buchwald, MD, PhD

Shlomo Koyman, MD

Thomas Galloway, MD

Bhisham Chere, MD

Upendra Parvathaneni, MD

The purpose of the study is to see if the combination of radiation therapy and cemiplimab immunotherapy is an effective treatment for people with locally advanced, unresectable CSCC.

A Study of Radiation Therapy and Cemiplimab for People With Skin Cancer

A Phase II, Multicenter, Single-Arm Clinical Trial of Radiotherapy and CeMiPlimAb: Rwlc ImmunoTherapy for Locally Advanced, Unresectable Cutaneous Squamous Cell Carcinoma: RAMPART

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary endpoint for this study is disease free survival at 18 months (week 78 +/- 3 weeks) after starting cemiplimab.

Memorial Sloan Kettering Cancer Center

Head and Neck Neoplasms

Docetaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

radiotherapy: 70Gy/35 fraction for 7 weeks chemotherapy: docetaxel 20mg/m2 and cisplatin 20mg/m2 weekly for 6 weeks

CCRT with weekly docetaxel & cisplatin

This phase II trial is evaluating the efficacy of concurrent chemoradiation therapy with weekly docetaxel and cisplatin combination regimen.

Many studies have shown the superiority of concurrent chemoradiotherapy over radiotherapy only in locally advanced head and neck cancer. Concurrent chemoradiotherapy with high dose cisplatin has been universally used regimen. In a large-scaled phase II trial, however, conducted by the European Organization for the Research and Treatment of Cancer (EORTC), docetaxel (100mg/m2) plus cisplatin (75mg/ m2) every three weeks regimen produced improved survival, nonetheless there was significant limitation to deliver full doses of treatment due to significant hematologic and non-hematologic toxicities. Previously, we showed the safety of the combination regimen of weekly docetaxel and cisplatin in concurrent chemoradiation treatment in a phase I study. We determined the MTD of docetaxel to be 20mg/m2 weekly when concurrently administered with conventional fractionation RT and weekly 20mg/m2 of cisplatin.

Concomitant Chemoradiotherapy (CCRT) With Weekly Docetaxel and Cisplatin for Locally Advanced Head and Neck Cancer

A Phase II Trial of Concurrent Chemoradiotherapy With Weekly Docetaxel and Cisplatin for Locally Advanced Head and Neck Cancer

Samsung Medical Center

Principal investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Circulating Biomarkers in Patients With Anal Cancer Treated With Induction Chemotherapy	NCT05233540	Anal Cancer Locally Advance... Oligometastatic... Circulating Tum... Human Papilloma...		18 Years -	Aarhus University Hospital
Circulating Biomarkers in Patients With Anal Cancer Treated With Induction Chemotherapy	NCT05233540	Anal Cancer Locally Advance... Oligometastatic... Circulating Tum... Human Papilloma...		18 Years -	Aarhus University Hospital
A Study of Radiation Therapy and Cemiplimab for People With Skin Cancer	NCT05574101	Cutaneous Squam... Skin Cancer Squamous Cell C... Locally Advance... Locally Advance... Locally Advance... Locally Advance...	Cemiplimab Radiotherapy	18 Years -	Memorial Sloan Kettering Cancer Center
Concomitant Chemoradiotherapy (CCRT) With Weekly Docetaxel and Cisplatin for Locally Advanced Head and Neck Cancer	NCT01126008	Head and Neck C...	CCRT with weekl...	18 Years -	Samsung Medical Center
Circulating Biomarkers in Patients With Anal Cancer Treated With Induction Chemotherapy	NCT05233540	Anal Cancer Locally Advance... Oligometastatic... Circulating Tum... Human Papilloma...		18 Years -	Aarhus University Hospital
A Study of Radiation Therapy and Cemiplimab for People With Skin Cancer	NCT05574101	Cutaneous Squam... Skin Cancer Squamous Cell C... Locally Advance... Locally Advance... Locally Advance... Locally Advance...	Cemiplimab Radiotherapy	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for locally advanced squamous cell carcinoma