Rectal CancerPhase 1NCT01407107
Dose Escalation Trial of Nitroglycerin, 5-flourouracil and Rad Therapy for Rectal Cancer
A Phase 1 study testing Nitroglycerin 0.2 MG/HR, Nitroglycerin 0.4 MG/HR and Nitroglycerin 0.6 MG/HR in people with Rectal Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Nitroglycerin 0.2 MG/HR, Nitroglycerin 0.4 MG/HR and Nitroglycerin 0.6 MG/HR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Oct 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dallas Veterans Affairs Medical Center
Dallas, Texas, 75216
About this study
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
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.
Read the 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.
- Conditions
- Rectal Cancer
- Being tested
- Nitroglycerin 0.2 MG/HR, Nitroglycerin 0.4 MG/HR, Nitroglycerin 0.6 MG/HR
- Keywords
- nitroglycerin, 5-flourouracil, radiation therapy, neo-adjuvant treatment
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitroglycerin 0.2 MG/HRDrug
0.2mg/hr nitroglycerin transdermal patch daily. The first 3 patients will have a low dose patch applied (0.2 mg/hr).
Nitroglycerin 0.4 MG/HRDrug
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 0.6 MG/HRDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Nitroglycerin | Experimental | Dose escalation trial of Nitroglycerin Receives: Drug: Nitroglycerin 0.2 MG/HR; Drug: Nitroglycerin 0.4 MG/HR; Drug: Nitroglycerin 0.6 MG/HR |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 4-6 weeks for each dosing cohort
Secondary outcomes (1)
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.
Measured: Time of surgery (~ 6-9 wks) following the completion of neoadjuvant therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2011 (estimated)
- Study startJan 2011
- Primary completionOct 2015
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- US Department of Veterans Affairs
- Responsible party
- Principal investigator, Jonathan E. Dowell, University of Texas Southwestern Medical Center
- Investigators
- Jonathan Dowell, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01407107
- Sponsor's protocol ID
- STU 122010-172
- Status last verified
- Dec 2020
- First submitted
- 29 Jul 2011
- Last updated
- 14 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01407107
- Acronym / sponsor ID
- STU 122010-172
- Conditions
- Rectal Cancer
- Keywords
- nitroglycerin, 5-flourouracil, radiation therapy, neo-adjuvant treatment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- US Department of Veterans Affairs
- Study start
- Jan 2011
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 1 Aug 2011 (estimated)
- Results
- Posted 14 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nitroglycerin | Experimental | Drug: Nitroglycerin 0.2 MG/HR, Drug: Nitroglycerin 0.4 MG/HR, Drug: Nitroglycerin 0.6 MG/HRDose escalation trial of Nitroglycerin |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitroglycerin 0.2 MG/HR0.2mg/hr nitroglycerin transdermal patch daily. The first 3 patients will have a low dose patch applied (0.2 mg/hr). | Drug | Nitroglycerin |
| Nitroglycerin 0.4 MG/HR0.4mg/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. | Drug | Nitroglycerin |
| Nitroglycerin 0.6 MG/HR0.6mg/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. | Drug | Nitroglycerin |
Primary outcome
The Number of Participants Experiencing Dose Limiting Toxicities (DLT)
Time frame: Up to 4-6 weeks for each dosing cohort
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
1 secondary outcome
Number of Participants With a Pathological Complete Response (pCR)
Time frame: Time of surgery (~ 6-9 wks) following the completion of neoadjuvant therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Dowell, MD principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nitroglycerin 0.2 MG/HR, Nitroglycerin 0.4 MG/HR and Nitroglycerin 0.6 MG/HR in people with Rectal Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Participants Experiencing Dose Limiting Toxicities (DLT) (time frame: Up to 4-6 weeks for each dosing cohort). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2021.