Dose Escalation Trial of Endoluminal High-Dose-Rate Brachytherapy With Concurrent Chemotherapy for Rectal or Anal Cancer in Patients With Recurrent Disease or Undergoing Non-Operative Management

A Phase I, Dose Escalation Trial of Endoluminal High Dose Rate Brachytherapy With Concurrent Chemotherapy for Rectal or Anal Cancer in Patients With Recurrent Disease or Undergoing Non-Operative Management

The purpose of this study is to see what amount of radiation is safe to give to rectal or anal cancer patients who are being treated with a procedure called brachytherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Rectal or Anal Cancer
• Intervention / Treatment: Radiation: endorectal brachytherapy; Drug: concurrent capecitabine or 5-FU; Behavioral: Questionnaires

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge (Follow Up Only)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Follow Up Only)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack (Consent and Follow up)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (Follow Up Only)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Rockville Center (Follow Up Only)
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (Follow-Up only)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed locally residual or recurrent cancer of the rectum or anus
• Prior pelvic EBRT
• Age > or = to 18 years
• ECOG performance status 0, 1, or 2
• At least 4 weeks from prior major surgery or radiotherapy

• Have undergone Surgical, Medical and Radiation Oncology evaluations to confirm :

  • Eligible for infusional 5-FU or capecitabine
  • Will not undergo surgery for the study disease
  • Able to receive HDR brachytherapy ANC ≥ 1.5 cells/mm3 and PLT ≥100,000/mm3
• Adequate Renal function: Creatinine <1.5 x the upper limit of normal (ULN) or calculated creatinine clearance of ≥ 50cc/min
• Adequate Hepatic functions: Bilirubin less than 1.5 mg/dL; (except in patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• AST or ALT <3xULN, or <5x ULN if known liver metastases

• Normal Cardiac function:

  • No active coronary artery disease;
  • No New York Heart Association class II, III or IV disease;
  • No arrhythmia requiring treatment
  • Maximum tumor length of 7 cm at time of brachytherapy treatment start

Exclusion Criteria:

• Women who are pregnant.
• Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire treatment period and after receipt of brachytherapy. Male subjects must also agree to use effective contraception during the treatment period and until 1 year after the completion of brachytherapy.
• Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment, would make them inappropriate candidates for entry into this study.
• Patients on concurrent anti-cancer therapy other than that allowed in the study.
• Contraindications to general anesthesia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: endorectal brachytherapy, concurrent chemo and questionnaires; This is a phase I, dose-escalation study to evaluate the safety of endorectal brachytherapy with concurrent capecitabine or 5-fluoruracil (5-FU) in the management of locally recurrent/residual rectal or anal cancer in patients who have received pelvic external beam radiation therapy (EBRT) +/- chemotherapy. We will use magnetic resonance imaging (MRI) with dynamic contrast enhancement (DCE) and diffusion weighted imaging (DWI) series to contribute to the assessment of tumor response.

Radiation: endorectal brachytherapy; Patients will receive 3 fractions of endorectal brachytherapy, each spaced apart by 7 days (+/- 1 day). The three dose tiers will be 1500cGy (500cGy per fraction), 1800cGy (600cGy per fraction), and 2100cGy (700cGy per fraction).; Drug: concurrent capecitabine or 5-FU; Patients will receive 500 mg and 150 mg oral tablets of capecitabine for the prescribed dose of 825 mg/m2 BID, morning and evening (total daily dose of 1650 mg/m2 ). Dosages will be rounded to the nearest 150 mg or 500 mg. Tablets should be swallowed with water within 30 minutes after a meal. Capecitabine will be started on the Monday of the first week of brachytherapy (day 1) and taken on weekdays (Monday through Friday) during weeks of brachytherapy only. Administration of 5-FU should be only by the intravenous route taking care to avoid extravasation. Patients will receive 225 mg/m2/day, as a continuous venous infusion by a portable pump for the 3 weeks of treatment. The infusional 5-FU will be exchanged every 7 days.; Behavioral: Questionnaires; Patients should complete the 2 quality of life questionnaires during their follow-up appointments. If they are unable to be seen in follow-up, they may complete the questionnaires at home and email or mail them back to the investigator. Should there be any incomplete or ambiguous answers, a follow-up phone call will be made by a member of the research team for clarification. Additionally, if the questionnaires have not been returned within 3 weeks after the time when they are due, a member of the research team will call the patient, and the questions will be completed over the phone.; Other Names: Quality of Life Assessment; Bowel Function Assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum tolerated dose (MTD)	will employ a standard 3+3 dose-escalation scheme. Patients will be accrued to the study in cohorts of 3. An initial cohort of 3 patients will be treated to each dose. The dose level will be escalated if none of the 3 patients exhibits any DLT within 90 days of completion of brachytherapy. Dose escalation will not take place until every patient in the prior dose cohort has been monitored for 90 days.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor response	MRI with DCE & DWI (unless contraindicated) after brachytherapy	3, 6, and 12 months

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Abraham Wu, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: July 22, 2014
• First Posted (Estimated): July 24, 2014

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Questionnaires; High-Dose-Rate Brachytherapy; oral capecitabine; infusional 5-FU; 14-104
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Anus Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: 14-104