Clinical trial NCT01407107: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rectal Cancer
Keywords: nitroglycerin
5-flourouracil
radiation therapy
neo-adjuvant treatment
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: US Department of Veterans Affairs
First posted: 2011-08-01
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The Number of Participants Experiencing Dose Limiting Toxicities (DLT)
timeFrame: Up to 4-6 weeks for each dosing cohort
Secondary outcomes:
measure: Number of Participants With a Pathological Complete Response (pCR)
timeFrame: Time of surgery (~ 6-9 wks) following the completion of neoadjuvant therapy
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Dallas Veterans Affairs Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Jonathan Dowell, MD
role: PRINCIPAL_INVESTIGATOR
References: