Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Anus Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Anal Cancer

BI 754091

BI 836880

The objective of this trial is to assess anti-tumour activity of BI 754091 as monotherapy and of BI 754091 in combination with BI 836880 in patients with unresectable or metastatic squamous cell carcinoma of the anal canal who progressed on or after chemotherapy.

A Study to Test BI 754091 Alone or in Combination With BI 836880 in People Who Have Advanced Anal Cancer

An Open Label, Randomized Phase II Study of BI 754091 Alone or in Combination With BI 836880 in Patients With Chemotherapy Resistant, Unresectable, Metastatic Squamous Cell Carcinoma of the Anal Canal

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

Boehringer Ingelheim

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Fluorouracil

Capecitabine

Mitomycins

Mitomycin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Patients undergo 28 fractions of intensity-modulated radiation therapy (IMRT). Within 24 hours, patients also receive mitomycin IV over 30 minutes or less on day 1 and either fluorouracil IV over 24 hours on days 1-4 and 29-32 or capecitabine PO BID 5 days per week (Monday - Friday) until completion of IMRT in the absence of disease progression or unacceptable toxicity.

Patients undergo 20 or 23 fractions of IMRT. Within 24 hours, patients also receive mitomycin IV over 30 minutes or less on day 1 and either fluorouracil IV over 24 hours on days 1-4 or capecitabine PO BID 5 days per week (Monday - Friday) until completion of IMRT in the absence of disease progression or unacceptable toxicity.

Intensity-Modulated Radiation Therapy

Quality-of-Life Assessment

Questionnaire Administration

Site Public Contact

Alison K. Conlin

Nicholas DiBella

John A. Ellerton

Shahzad Siddique

Jay W. Carlson

James D. Murphy

Jason A. Zell

Tyler Robin

Gregory A. Masters

Anteneh A. Tesfaye

Lorraine Portelance

Michael D. Chuong

Patrick Kelly

Sudha R. Amarnath

John M. Schallenkamp

Daniel H. Barnett

Bryan A. Faller

Sheetal M. Kircher

Thomas Kim

Yolande Chen

Jennifer A Dorth

This phase II trial studies how well lower-dose chemotherapy plus radiation (chemoradiation) therapy works in comparison to standard-dose chemoradiation in treating patients with early-stage anal cancer. Drugs used in chemotherapy, such as mitomycin, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells. This study may help doctors find out if lower-dose chemoradiation is as effective and has fewer side effects than standard-dose chemoradiation, which is the usual approach for treatment of this cancer type.

PRIMARY OBJECTIVES:

I. To determine whether de-intensified chemoradiation for early stage squamous cell carcinoma of the anal canal (SCCA) is able to maintain excellent 2-year disease control of 85% or higher while improving anorectal health-related quality of life (HRQL), compared to standard-dose chemoradiation therapy (CRT), as measured by the change in the Fecal Incontinence Quality of Life scale (FIQoL) instrument coping/behavior domain from baseline to 1 year.

SECONDARY OBJECTIVES:

I. To compare changes in patient-reported outcomes (as per Fecal Incontinence Severity Index \[FISI\], Patient Reported Outcomes Measurement Information System \[PROMIS\], International Index of Erectile Function \[IIEF\], Sexual Function-Vaginal Changes Questionnaire \[SVQ\], and Vaginal Assessment Scale \[VAS\]/Vulvar Assessment Scale \[VuAS\] instruments) between the experimental and control arm.

II. To compare patterns of failure (local and regional relapse versus distant; in-field versus out-of-field of radiation), disease control, and overall survival between experimental and control arm.

III. To correlate vaginal dilator use during radiation delivery with sexual function.

IV. To measure changes in serum total testosterone from baseline to up to 12 months after radiation.

V. To validate the utility of image features of inguinal and pelvic lymph nodes obtained prior to treatment as a prognostic indicator that can identify patients with early-stage anal squamous cell carcinoma for whom treatment with de-intensified chemoradiation is appropriate.

VI. To determine whether an online, interactive educational tool (eContour) may improve the quality of radiation target delineation for anal cancer.

VII. To determine the incidence of and predictors for cardiovascular toxicity in patients receiving fluorouracil (5-FU) or capecitabine.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A (STANDARD-DOSE CHEMORADIATION): Patients undergo 28 fractions of intensity-modulated radiation therapy (IMRT). Within 24 hours, patients also receive mitomycin intravenously (IV) over 30 minutes or less on day 1 and either fluorouracil IV over 24 hours on days 1-4 and 29-32 or capecitabine orally (PO) twice daily (BID) 5 days per week (Monday - Friday) until completion of IMRT in the absence of disease progression or unacceptable toxicity.

ARM B (DE-INTENSIFIED CHEMORADIATION): Patients undergo 20 or 23 fractions of IMRT. Within 24 hours, patients also receive mitomycin IV over 30 minutes or less on day 1 and either fluorouracil IV over 24 hours on days 1-4 or capecitabine PO BID 5 days per week (Monday - Friday) until completion of IMRT in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 weeks, every 3 months for years 1-2, every 6 months for year 3, then annually for years 4-5.

Lower-Dose Chemoradiation in Treating Patients With Early-Stage Anal Cancer, the DECREASE Study

A Randomized Phase II Study De-Intensified ChemoRadiation for Early-Stage Anal Squamous Cell Carcinoma (DECREASE)

Will be compared between experimental and control arm. Will be estimated for all treatment arms using the Kaplan-Meier method (1958).

An event is local-regional failure, distant metastasis and chemoradiation-related death. Will determine if de-intensified chemoradiation achieves 2-year disease control of 85% or higher while improving anorectal health-related quality of life (HRQL), compared to standard-dose CRT, as measured by the change in the Fecal Incontinence Quality of Life scale (FIQoL) instrument coping/behavior domain from baseline to 1 year. The co-primary endpoints of disease control and FIQoL will be formally assessed in a hierarchical manner with disease control being assessed first. Will be estimated for all treatment arms using the Kaplan-Meier method (1958).

Quality of life analyses, will be compared between arms using a two-sample independent t-tests at a significance level of 0.05 and appropriate longitudinal models will be evaluated to assess the trajectory of HRQL endpoints over time and to evaluate those trajectories between treatment arms. Overall score and change from baseline will be summarized using mean and standard deviation at each time point for each arm.

Will compare changes as per HRQL: Health Related Quality of Life FACT-G (Functional Assessment of Cancer Therapy-General - Scoring: 0 - 32 with higher worse) between the experimental and control arm. Quality of life analyses, will be compared between arms using a two-sample independent t-tests at a significance level of 0.05 and appropriate longitudinal models will be evaluated to assess the trajectory of HRQL endpoints over time and to evaluate those trajectories between treatment arms. Overall score and change from baseline will be summarized using mean and standard deviation at each time point for each arm.

Will compare changes as per Fecal Incontinence Severity Index \[FISI - Scoring: 0 - 61 with lower better\] between the experimental and control arm.

Will compare changes as per International Index of Erectile Function \[IIEF\], Erectile Dysfunction: Scoring 7 - 35 with lower better. Ejaculation Frequency: Scoring 1 - 5 with lower better - between the experimental and control arm.

Will compare changes as per Orgasm ability/pleasure (PROMIS-Brief): scoring 2 - 10 with lower better - between the experimental and control arm.

PROMIS = Patient Reported Outcomes Measurement Information System

Will compare changes as per Anal Discomfort/pain (PROMIS- Full): scoring 3 - 15 with lower better. - between the experimental and control arm.

PROMIS = Patient Reported Outcomes Measurement Information System

Will compare changes as per Satisfaction with sex life (PROMIS-Brief) (scoring 2 - 10 with higher better) between the experimental and control arm.

PROMIS = Patient Reported Outcomes Measurement Information System

Will compare changes as per Therapeutic Aids for Sexual Function - Male (Scoring 6 - 22 with lower better) between the experimental and control arm.

Will compare changes as per Therapeutic Aids for Sexual Function - Female (Scoring 5 - 17 with lower better) between the experimental and control arm.

Will compare changes as per Sexual Function-Vaginal Changes Questionnaire \[SVQ\] (Scoring 5 - 26 with higher better) between the experimental and control arm.

Will compare changes as per Vaginal Assessment Scale \[VAS\]/Vulvar Assessment Scale \[VuAS\] (Scoring:0 - 22 with lower better) between the experimental and control arm.

Will be compared between experimental and control arm. The cumulative incidence method will be used to estimate local-regional and distant failure rates and the failure rates for the experimental treatment will be compared against the control using a failure specific log rank test.

Vaginal dilator use during radiation delivery will be correlated with sexual function.

Will be validated as a prognostic indicator that can identify patients with early-stage anal squamous cell carcinoma for whom treatment with de-intensified CRT is appropriate.

Will determine whether an online, interactive educational tool (eContour) may improve the quality of radiation target delineation for anal cancer.

Rates of grade 3+ adverse events (Common Terminology Criteria for Adverse Events \[CTCAE\], version \[v.\] 5) will be estimated using a binomial distribution along with their associated 95% confidence intervals and compared using Fisher's exact test between arms.

National Cancer Institute (NCI)

ECOG-ACRIN Cancer Research Group

Symptoms and General Pathology

Neoplasm Metastasis

Esophageal Squamous Cell Carcinoma

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Esophageal Neoplasms

Esophageal Diseases

Esophageal Cancer

Immunomodulating Agents

Patients with a histological or cytological confirmed diagnosis of Squamous Cell Cancer of the Head \& Neck, Esophagus or Anal Canal who have radiologically confirmed recurrent or metastatic disease and are commencing on a new treatment or either first-line platinum based chemotherapy or any line immunotherapy.

Elena Elimova, MD

This is prospective research study which will include patients with recurrent or metastatic squamous cell carcinoma of the head and neck, esophagus and anal canal starting on first-line platinum based chemotherapy or any line of immunotherapy treatment.This study aims to characterize the dynamic changes in genomic, epigenetic, immune profiling and imaging data during treatment with systemic therapy. Patients will have archived tumor samples requested as well as blood samples collected at up to four time points to analyze these changes. Imaging data will be derived from patients' routine CT scans before and after treatment.

Peripheral blood samples collected serially for DNA extraction under the LIBERATE protocol. Archived tumor samples collected for DNA extraction.

Multi-Omic Assessment of Squamous Cell Cancers Receiving Systemic Therapy

To comprehensively characterize genomic, epigenetic and immune profiling features and changes in longitudinal blood samples that are associated with systemic treatment of recurrent or metastatic squamous cell cancers of the head \& neck, esophagus and anal canal.

To establish a clinically annotated biorepository of archived tumor and longitudinal blood samples, with serial radiomic evaluations in patients with recurrent/metastatic squamous cell cancers commencing on any new systemic treatments.

To correlate genomic, othr-omic, radiomic and immune profiling results with clinical outcome - to identify potential predictive markers of response/resistance to systemic therapy.

To compare HPV-positive and HPV-negative squamous cell histology across three disease sites with multi-omic assessment.

To investigate whether any correlation or relation exists between tumor genomic profiles and radiomic imaging signatures.

To enable data sharing with Queen's University Belfast as a collaborative initiative based on this project

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Test BI 754091 Alone or in Combination With BI 836880 in People Who Have Advanced Anal Cancer	NCT04499352	Anal Canal Squa...	BI 754091 BI 836880	18 Years -	Boehringer Ingelheim
Lower-Dose Chemoradiation in Treating Patients With Early-Stage Anal Cancer, the DECREASE Study	NCT04166318	Anal Basaloid C... Anal Canal Cloa... Anal Canal Squa... Anal Margin Squ... Stage I Anal Ca... Stage IIA Anal ...	Capecitabine Fluorouracil Intensity-Modul... Mitomycin Quality-of-Life... Questionnaire A...	18 Years -	Eastern Cooperative Oncology Group
Multi-Omic Assessment of Squamous Cell Cancers Receiving Systemic Therapy	NCT03712566	Cancer Esophagus Squam... Squamous Cell C... Anal Canal Squa... Metastatic Canc...		18 Years -	University Health Network, Toronto

Spots Global Cancer Trial Database for anal canal squamous cell carcinoma