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Dose Escalation Trial of Nitroglycerin, 5-flourouracil and Rad Therapy for Rectal Cancer

Primary Purpose

Rectal Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nitroglycerin 0.2 MG/HR
Nitroglycerin 0.4 MG/HR
Nitroglycerin 0.6 MG/HR
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring nitroglycerin, 5-flourouracil, radiation therapy, neo-adjuvant treatment

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Biopsy proven Rectal Adenocarcinoma
  • Histological diagnosis of operable T3-4, or T1-4 node positive, M0 rectal adenocarcinoma using endorectal ultrasound and/or MRI in addition to Computed Tomography (CT) of the chest, abdomen and pelvis for pre-study staging Acceptable alternatives for systemic staging instead of CT chest , abdomen, pelvis are CT abdomen and pelvis plus a Chest X-ray or a PET/CT
  • Ability to give informed consent and willingness to adhere to study protocol
  • Age ≥ 18 years and otherwise eligible to receive medical care at the Dallas VA Medical Center.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Adequate hematological, hepatic and renal function defined as in protocol.

Exclusion Criteria:

  • Any condition that would hamper informed consent or ability to comply with the study protocol
  • Significant history of cardiac disease, e.g. uncontrolled hypertension, unstable angina, decompensated congestive-heart failure, myocardial infarction within the last six months or ventricular arrhythmias requiring medication.
  • Pregnant and lactating women.
  • Patients taking Phosphodiesterase - 5 inhibitors (e.g. Sildenafil, Vardenafil or Tadalafil) and is unable to stop for the duration of the chemoradiotherapy.

Sites / Locations

  • Dallas Veterans Affairs Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nitroglycerin

Arm Description

Dose escalation trial of Nitroglycerin

Outcomes

Primary Outcome Measures

The Number of Participants Experiencing Dose Limiting Toxicities (DLT)
DLT was defined as greater or equal to two instances of grade 3 toxicity, or a single event of grade 4-5 toxicity deemed probably or definitely related to the addition of transdermal neoadjuvant chemoradiation to the standard neoadjuvant chemoradiation

Secondary Outcome Measures

Number of Participants With a Pathological Complete Response (pCR)
pathological complete response (pCR) at time of surgery following the completion of neoadjuvant therapy. This will be compared to the institutional historical pCR rate. Pathologic complete response indicates a complete absence of cancer at the time of surgical resection.

Full Information

First Posted
July 29, 2011
Last Updated
December 21, 2020
Sponsor
University of Texas Southwestern Medical Center
Collaborators
US Department of Veterans Affairs
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1. Study Identification

Unique Protocol Identification Number
NCT01407107
Brief Title
Dose Escalation Trial of Nitroglycerin, 5-flourouracil and Rad Therapy for Rectal Cancer
Official Title
Phase I Dose Escalation Trial of Nitroglycerin in Addition to 5-flourouracil and Radiation Therapy for Neo-adjuvant Treatment of Operable Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
US Department of Veterans Affairs

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether topical nitroglycerin in addition to 5-flourouracil and radiation therapy are effective in the treatment of operable rectal cancer.
Detailed Description
This is an open label, non-randomized, multi-cohort, dose escalation trial to evaluate the safety, tolerability, feasibility and maximum tolerated dose (MTD) of topical nitroglycerin in addition to 5-flourouracil and radiation therapy for neo-adjuvant treatment of, T3-T4 or clinically node positive, operable rectal cancer. Patients that would otherwise be eligible for concurrent neo-adjuvant chemotherapy with continuous infusion 5-FU, for locally advanced operable rectal cancer, will be assigned to 4 sequential cohorts of 3 different dose levels of nitro glycerin patches (0.2; 0.4; and 0.6 mg/hr). Each cohort will consist of 3 patients. All patients will receive radiation therapy, 45-50 Gy in 25-28 fractions to the pelvis along with continuous infusion 5-FU 225mg/M2 for the duration of the radiation therapy. The radiation therapy will be planned and delivered as per institutional standard of care for the Dallas VAMC radiation oncology department.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
nitroglycerin, 5-flourouracil, radiation therapy, neo-adjuvant treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nitroglycerin
Arm Type
Experimental
Arm Description
Dose escalation trial of Nitroglycerin
Intervention Type
Drug
Intervention Name(s)
Nitroglycerin 0.2 MG/HR
Intervention Description
0.2mg/hr nitroglycerin transdermal patch daily. The first 3 patients will have a low dose patch applied (0.2 mg/hr).
Intervention Type
Drug
Intervention Name(s)
Nitroglycerin 0.4 MG/HR
Intervention Description
0.4mg/hr nitroglycerin transdermal patch daily. The first 3 patients will have a low dose patch applied (0.2 mg/hr) if this is well tolerated a higher dose patch (0.4mg/hr) will be used for the next 3 patients.
Intervention Type
Drug
Intervention Name(s)
Nitroglycerin 0.6 MG/HR
Intervention Description
0.6mg/hr nitroglycerin transdermal patch daily. The first 3 patients will have a low dose patch applied (0.2 mg/hr) if this is well tolerated a higher dose patch (0.4mg/hr) will be used for the next 3 patients and if this is well tolerated an even higher dose patch (0.6mg/hr) will be used.
Primary Outcome Measure Information:
Title
The Number of Participants Experiencing Dose Limiting Toxicities (DLT)
Description
DLT was defined as greater or equal to two instances of grade 3 toxicity, or a single event of grade 4-5 toxicity deemed probably or definitely related to the addition of transdermal neoadjuvant chemoradiation to the standard neoadjuvant chemoradiation
Time Frame
Up to 4-6 weeks for each dosing cohort
Secondary Outcome Measure Information:
Title
Number of Participants With a Pathological Complete Response (pCR)
Description
pathological complete response (pCR) at time of surgery following the completion of neoadjuvant therapy. This will be compared to the institutional historical pCR rate. Pathologic complete response indicates a complete absence of cancer at the time of surgical resection.
Time Frame
Time of surgery (~ 6-9 wks) following the completion of neoadjuvant therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Biopsy proven Rectal Adenocarcinoma Histological diagnosis of operable T3-4, or T1-4 node positive, M0 rectal adenocarcinoma using endorectal ultrasound and/or MRI in addition to Computed Tomography (CT) of the chest, abdomen and pelvis for pre-study staging Acceptable alternatives for systemic staging instead of CT chest , abdomen, pelvis are CT abdomen and pelvis plus a Chest X-ray or a PET/CT Ability to give informed consent and willingness to adhere to study protocol Age ≥ 18 years and otherwise eligible to receive medical care at the Dallas VA Medical Center. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 Adequate hematological, hepatic and renal function defined as in protocol. Exclusion Criteria: Any condition that would hamper informed consent or ability to comply with the study protocol Significant history of cardiac disease, e.g. uncontrolled hypertension, unstable angina, decompensated congestive-heart failure, myocardial infarction within the last six months or ventricular arrhythmias requiring medication. Pregnant and lactating women. Patients taking Phosphodiesterase - 5 inhibitors (e.g. Sildenafil, Vardenafil or Tadalafil) and is unable to stop for the duration of the chemoradiotherapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Dowell, MD
Organizational Affiliation
UT Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dallas Veterans Affairs Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Dose Escalation Trial of Nitroglycerin, 5-flourouracil and Rad Therapy for Rectal Cancer

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