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

NCT01407107 | Completed Phase 1 Results DMC

• 1 other identifier: STU 122010-172
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Cancer

Keywords

nitroglycerin; 5-flourouracil; radiation therapy; neo-adjuvant treatment

Outcome Measures

Primary Outcomes (1)

• 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

  Up to 4-6 weeks for each dosing cohort

Secondary Outcomes (1)

• Number of Participants With a Pathological Complete Response (pCR)

  Time of surgery (~ 6-9 wks) following the completion of neoadjuvant therapy

Study Arms (1)

Nitroglycerin

EXPERIMENTAL

Dose escalation trial of Nitroglycerin

Drug: Nitroglycerin 0.2 MG/HR; Drug: Nitroglycerin 0.4 MG/HR; Drug: Nitroglycerin 0.6 MG/HR

Interventions

Nitroglycerin 0.2 MG/HR DRUG

0.2mg/hr nitroglycerin transdermal patch daily. The first 3 patients will have a low dose patch applied (0.2 mg/hr).

Nitroglycerin

Nitroglycerin 0.4 MG/HR DRUG

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.

Nitroglycerin

Nitroglycerin 0.6 MG/HR DRUG

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.

Nitroglycerin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• US Department of Veterans Affairs: collaborator

Study Sites (1)

Dallas Veterans Affairs Medical Center

Dallas, Texas, 75216, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Nitroglycerin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals

Results Point of Contact

• Title: Dr. Jonathan Dowell
• Organization: University of Texas Southwestern Medical Center

jonathan.dowell@utsouthwestern.edu

214-648-7097

Study Officials

• Jonathan Dowell, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 29, 2011
• First Posted: August 1, 2011
• Study Start: January 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2016
• Last Updated: January 14, 2021
• Results First Posted: January 14, 2021

Record last verified: 2020-12

Locations

US (1)