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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Texas Southwestern Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01407107
First received: July 29, 2011
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Rectal Cancer
Drug: nitroglycerin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: 4-6 weeks ] [ Designated as safety issue: Yes ]
    4 different dose levels of nitro glycerin patches (0.2; 0.4; 0.6 and 0.8mg/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.


Secondary Outcome Measures:
  • Pathological complete response (pCR) [ Time Frame: Time of surgery (~ 6-9 wks) following the completion of neoadjuvant therapy ] [ Designated as safety issue: No ]
    pathological complete response (pCR) at time of surgery following the completion of neoadjuvant therapy. This will be compared to the institutional historical pCR rate.


Estimated Enrollment: 24
Study Start Date: January 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nitroglycerin
Dose escalation trial of Nitroglycerin
Drug: nitroglycerin
0.2mg/hr nitroglycerin transdermal patch daily

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 4 different dose levels of nitro glycerin patches (0.2; 0.4; 0.6 and 0.8mg/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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01407107

Contacts
Contact: Sharjeel Farooqui 214-857-4237 sharjeely.farooqui@va.gov

Locations
United States, Texas
Dallas Veterans Affairs Medical Center Recruiting
Dallas, Texas, United States, 75216
Contact: Sharjeel Farooqui    214-857-4237    sharjeely.farooqui@va.gov   
Principal Investigator: Henrik Illum, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Jonathan Dowell, MD UT Southwestern Medical Center
  More Information

No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01407107     History of Changes
Other Study ID Numbers: VA10-100
Study First Received: July 29, 2011
Last Updated: September 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
nitroglycerin
5-flourouracil
radiation therapy
neo-adjuvant treatment

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Nitroglycerin
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 30, 2014