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

The University of Texas System (UT)

Status and phase

Completed

Phase 1

Conditions

Rectal Cancer

Treatments

Drug: Nitroglycerin 0.4 MG/HR

Drug: Nitroglycerin 0.2 MG/HR

Drug: Nitroglycerin 0.6 MG/HR

Study type

Interventional

Funder types

Other

Other U.S. Federal agency

Identifiers

NCT01407107

STU 122010-172

Details and patient eligibility

About

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.

Full 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.

Enrollment

13 patients

Sex

All

Ages

18 to 90 years old

Volunteers

No 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.