Predicting Disease Progression and/or Recurrence in Cancer

• ClinicalTrials.gov Identifier: NCT04776837
• Recruitment Status: Recruiting
• First Posted: March 2, 2021
• Last Update Posted: March 2, 2021
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Aparna Parikh, Massachusetts General Hospital

Study Description

Brief Summary:

This is a prospective study addressing the challenge of predicting disease progression and/or recurrence in patients diagnosed with metastatic colorectal, pancreatobiliary, or esophagogastric cancer that are receiving anti-cancer therapy.

Condition or disease	Intervention/treatment
Patient Reported Outcome Measures; Colorectal Cancer; Pancreatic Cancer; Biliary Tract Cancer; Esophageal Cancer; Metastatic Cancer; Disease Progression; Survival Analysis	Behavioral: Observational Cohort

Detailed Description:

This research study is evaluating how patient-reported outcomes (e.g. symptoms, quality of life) and biomarkers compare to standard of care clinical assessments such as imaging and tumor markers in predicting the clinical outcomes (e.g. disease progression and survival) in patient populations with colorectal, pancreatobiliary, or esophagogastric cancer that are receiving anti-cancer therapy Massachusetts General Hospital Cancer Center

• Patient reported outcomes will be collected through a series of self-administered questionnaires and blood draws will be used to obtain bio and tumor marker information.
• Information will also be collected from the participants electronic medical record.
• Tissue may be obtained for next-generation sequencing.
• The study will conclude after participants are no longer receiving anti-cancer therapies.
• It is expected that about 600 people will take part in this research study

Study Design

• Study Type: Observational
• Estimated Enrollment: 600 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Tumor Markers, Liquid Biopsies, and Patient Reported Outcomes in Metastatic Colorectal, Pancreas, Biliary, and Esophagogastric Cancers
• Actual Study Start Date: April 30, 2019
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: April 2024

Groups and Cohorts

Group/Cohort

Intervention/treatment

Main Cohort; Patient-reported outcomes (e.g. symptoms, quality of life) and biomarkers compare to standard of care clinical assessments such as imaging and tumor markers in predicting the clinical outcomes (e.g. disease progression and survival); Prior to starting anti-cancer therapy and at subsequent designated visits (every one month); Collections include: Blood sample Questionnaires quality of life, mood, and symptoms Tissue may be obtained for next-generation sequencing.

Behavioral: Observational Cohort; Patients will be followed by collecting clinical data, biospecimens, and quality of life assessment

Outcome Measures

Primary Outcome Measures :

1. Treatment Response at 1st Scan [ Time Frame: 6 months ]
   The primary outcome is treatment response (RECIST 1.1) at first scan (>1 month post-treatment start). Both response status (PR vs SD or PD [including death]) and clinical benefit status (PR or SD vs PD [including death]) will be examined. Primary analyses will compare one month change from baseline in tumor markers, MAF of the selected clonal mutation in ctDNA, and PROs (symptoms, mood, and QOL) individually and a composite score in predicting response and clinical benefit (CB) at first scan.

Secondary Outcome Measures :

1. Treatment Response at 1st Scan - Continuous Outcome [ Time Frame: 6 months ]
   Change from baseline to one month for each variable (tumor markers [CEA, CA19-9], ctDNA, and PROs [symptoms, mood, QOL]) will be evaluated individually as a predictor of percent change in tumor measurements at first scan (RECIST 1.1).
2. Progression Free Survival - KMC [ Time Frame: 1 year ]
   Estimate distributions of progression free survival using the Kaplan-Meier method.
3. Progression Free Survival - HR [ Time Frame: 1 year ]
   Use Cox proportional hazards models to obtain hazard ratios for Progression Free Survival for change in tumor markers, ctDNA and PROs.
4. Overall Survival - KMC [ Time Frame: 1 year ]
   Estimate distributions of overall survival using the Kaplan-Meier method.
5. Overall Survival - HR [ Time Frame: 1 year ]
   Use Cox proportional hazards models to obtain hazard ratios for Overall Survival for change in tumor markers, ctDNA and PROs.
6. ROC Curves [ Time Frame: 1 year ]
   The investigators will compare the predictive ability of change in tumor markers, ctDNA, and PROs in these models using time-dependent ROC curves evaluated at specific timepoints including 6 and 12 months.
7. PROs and Biomarkers as predictor of survival using cox proportional hazards model [ Time Frame: 6 months ]
   The investigators will run multivariable Cox proportional hazards regression with purposeful selection of covariates to explore combinations of variables (change in tumor markers [CEA, CA19-9], ctDNA, and PROs [symptoms, mood, QOL]) as predictors of survival (PFS and OS).
8. Association between baseline PROs, biomarkers and tumor response [ Time Frame: 6 months ]
   The investigators will look at correlations between baseline ctDNA levels, baseline tumor markers and baseline PRO assessments and tumor response.
9. Associations between baseline PROs, biomarkers, and 6-month survival outcomes [ Time Frame: 6 months ]
   The investigators will look at correlations between baseline ctDNA levels, baseline tumor markers and baseline PRO assessments and 6-month survival outcomes (PFS, OS)
10. Sarcopenia Analysis [ Time Frame: 1 year ]
    As an exploratory outcome the investigators will compare differences in demographic and clinical characteristics, PROs, and clinical outcomes, between patients with and without sarcopenia.
11. Skeletal Muscle Analyses [ Time Frame: 1 year ]
    As an exploratory outcome the investigators will compare differences in demographic and clinical characteristics, PROs, and clinical outcomes, between patients by skeletal muscle index and density.

Biospecimen Retention:   Samples With DNA

Blood samples will be collected serially throughout study treatment. It will be processed to separate blood cell pellet from plasma and each component will be aliquoted and frozen for subsequent analyses.

Tissue will be obtained for next-generation sequencing from formalin fixed archival tumor.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients must have histologically confirmed colorectal, pancreatobiliary, or esophagogastric cancer and receiving anti cancer treatment at Massachusetts General Hospital Cancer Center

Criteria

• Inclusion Criteria:

  • Patients must have histologically confirmed colorectal, pancreatobiliary, or esophagogastric cancer.
  • Diagnosed with metastatic disease
  • Age > 18 years.
  • Patients must be starting new line of anti-cancer therapy.
  • Patient must be English-speaking.
• Exclusion Criteria
• Unwilling or unable to participate in the study
• Non-metastatic disease
• Not starting new anti-cancer treatment
• Cognitive issues interfering with ability to participate.
• Active, unstable, untreated serious mental illness interfering with ability to participate.
• Patient does not speak English.

Contacts and Locations

Contacts

Contact: Aparna R Parikh, MD, MS; (617) 724-4000; aparna.parikh@mgh.harvard.edu

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Aparna R Parikh, MD, MS 617-724-4000 aparna.parikh@mgh.harvard.edu

Principal Investigator: Aparna R Parikh, MD, MS

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Aparna R Parikh, MD, MS; Massachusetts General Hospital

More Information

• Responsible Party: Aparna Parikh, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT04776837
• Other Study ID Numbers: 18-380
• First Posted: March 2, 2021
• Last Update Posted: March 2, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 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 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
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aparna Parikh, Massachusetts General Hospital:

Patient Reported Outcome Measures; Colorectal Cancer; Pancreatic Cancer; Biliary Tract Cancer; Esophageal Cancer; Metastatic Cancer; Disease Progression; Survival Analysis

Additional relevant MeSH terms:

Colorectal Neoplasms; Pancreatic Neoplasms; Esophageal Neoplasms; Neoplasm Metastasis; Biliary Tract Neoplasms; Disease Progression; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Disease Attributes; Pathologic Processes; Head and Neck Neoplasms; Esophageal Diseases; Neoplastic Processes; Biliary Tract Diseases