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Anal CancerPhase 1NCT01324141

Topical MTS-01 for Dermatitis During Radiation and Chemotherapy for Anal Cancer

A Phase 1 study testing Tempol, 5-Fluorouracil and Mitomycin-C in people with Anal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Background: Radiation and chemotherapy treatments for anal cancer can cause irritation of the skin that can lead to redness and tenderness, and in some cases can be so severe that it results in blistering or peeling of the skin during treatment. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Anal Cancer
What is being tested?
Tempol, 5-Fluorouracil and Mitomycin-C
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
18 Mar 2011to 15 Apr 2015
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

  • Histologically proven, invasive primary squamous, basaloid, or cloacogenic carcinoma of the anal canal, stage T1-4, N0-3
  • No previous therapy for anal cancer.
  • Age greater than or equal to 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
  • Adequate bone marrow, renal, and hepatic function defined as
  • Absolute neutrophil count greater than or equal to 1,000 cells/mm(3)
Show all 15Show fewer
  • Platelet count greater than or equal to 100,000/mm(3)
  • Hemoglobin greater than or equal to 8mg/dL
  • Creatinine clearance > 60 mL/min using Cockcroft-Gault formula
  • Bilirubin less than or equal to 1.5 times upper limit of normal (ULN) unless, during screening, the patient is receiving protease inhibitor therapy (i.e. indinavir, ritonavir, nelfinavir, and atazanavir) known to be associated with increased bilirubin: in this case total bilirubin less than or equal to 7.5 mg/dl and the direct fraction is less than or equal to 0.7 mg/dl.
  • White blood cell (WBC) greater than or equal to 3,000/microL
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to 3 times the upper limit of normal
  • International normalized ratio (INR) less than or equal to 1.5
  • Patients of childbearing potential must be willing to use a medically effective means of birth control for the duration of treatment and six weeks after treatment.
  • Patients must be willing and able to provide informed consent

Who cannot join

  • Contraindications to radiotherapy such as a history of prior radiotherapy to the pelvis or a history of inflammatory bowel disease
  • Prior malignancy except:
  • non-melanoma skin cancer
  • controlled Kaposi's Sarcoma (no chemotherapy for KS for 3 months, and no expected need for chemotherapy for the 12-month period of the study)
  • other malignancies with disease free period of at least 3 years
  • Presence of metastatic disease (M1)
Show all 10Show fewer
  • Co-morbidity that in the estimation of the principal investigator would make the patient unable to tolerate treatment
  • Pregnant or lactating females
  • Human immunodeficiency virus (HIV) positive patients with cluster of differentiation 4 (CD4) < 100 cells/mL AND ECOG performance status (PS) greater than 2.
  • Dermatitis in the anticipated radiation treatment portal.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Pilot Trial Assessing the Feasibility of Delivering Topical MTS-01 to Reduce Dermatitis in Patients Receiving Intensity Modulated Radiation With Concurrent 5-Fluorouracil and Mitomycin-C for Stage I-III Carcinoma of the Anal Canal

Background:

  • Radiation and chemotherapy treatments for anal cancer can cause irritation of the skin that can lead to redness and tenderness, and in some cases can be so severe that it results in blistering or peeling of the skin during treatment. These conditions cause discomfort and may require breaks from radiation treatment. Researchers are interested in determining whether MTS-01, a drug that protects cells and tissues from the effects of radiation, can be given before radiation treatment to prevent these side effects and reduce the irritation of the skin during chemotherapy and radiation for anal cancer.
Read more

Objectives:

  • To determine the safety and effectiveness of topical MTS-01 given before radiation in the groin and gluteal cleft of patients receiving combined radiation and chemotherapy for anal cancer.

Eligibility:

  • Individuals at least 18 years of age who have been diagnosed with cancer of the anal canal and are eligible to receive radiation and chemotherapy treatments.

Design:

  • Participants will be screened with a physical examination, medical history, blood tests, imaging studies and physical examination of the anal canal, and biopsies as needed to evaluate eligibility for treatment.
  • Participants will be scheduled for radiation and chemotherapy treatments on the following schedule:
  • Radiation given 5 days per week for 6 weeks, with topical MTS-01 treatment on the skin in the groin areas and between the buttocks before each treatment
  • Mitomycin C given intravenously on days 1 and 29 of treatment
  • 5-Fluorouracil given intravenously over 4 days (first week and fifth week) during radiation treatment
  • Participants will be monitored throughout the treatment for side effects, with photographs of the treatment area and frequent blood tests.
  • Following the end of radiation, participants will have followup visits for 1 year with blood tests and imaging studies to evaluate the response to treatment.
Read the detailed description

Background:

  • Patients with non-metastatic carcinoma of the anal canal are treated with concurrent mitomycin C (MMC), 5-fluorouracil (5-FU), and radiotherapy (RT) in the curative setting in an attempt to preserve the anal sphincter.
  • Radiation dermatitis is a uniform complication of this therapy which frequently results in treatment delay due to pain and discomfort. High grade dermatitis may also become superinfected in the setting of decreased blood counts from chemotherapy and diarrhea from radiation proctitis, further delaying therapy. Approaches that decrease toxicity may be particularly important in patients infected with human immunodeficiency virus (HIV).
  • MTS-01 (tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a piperidine nitroxide known to act as a chemical radioprotector with selective protection of normal versus tumor tissue.
  • Tempol gel (tempol 70 mg/mL plus water, ethanol, and hydroxypropyl cellulose) has been evaluated as a topical radioprotector in pilot trials that included a variety of sites.

Objectives:

  • Primary Objective: To determine the safety and tolerability of topical MTS-01 on a daily basis prior to irradiation in the groin and gluteal cleft of patients receiving combined therapy with MMC, 5-FU, and RT for carcinoma of the anal canal.
  • Secondary Objectives will include evaluation of the following endpoints in a preliminary fashion:
  • To describe the rates and severity of skin toxicity in patients treated with this regimen
  • To describe the need for toxicity related treatment breaks with this regimen
  • To describe the opiate requirements in patients treated with this regimen
  • To describe 12-month progression-free survival, disease-free survival, and overall survival in patients treated with concurrent chemotherapy, radiation therapy, and MTS-01
  • Evaluate the effects of antiretroviral therapy, 5-fluorouracil, mitomycin C, and radiation on low level persistent HIV viremia and HIV genetic diversity during therapy and recovery
  • To evaluate the feasibility of collecting HIV ribonucleic acid (RNA) and mononuclear cells from rectal associated lymphoid tissue for correlative studies
  • Collect and store anal cytology and core needle biopsies of tumor for future human papillomavirus infection (HPV) and tumor based analyses

Eligibility:

  • Age greater than or equal to 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
  • Histologically confirmed carcinoma of the anal canal without evidence of distant metastases
  • No contraindications to definitive chemoradiotherapy for carcinoma of the anal canal

Design:

This is a pilot trial of topical MTS-01 in patients receiving MMC, 5-FU, and intensity-modulated radiation therapy (IMRT) for definitive management of carcinoma of the anal canal. Fifteen patients will be enrolled. MMC will be delivered at a dose of 10mg/m(2) on days 1 and 29. 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. RT will be delivered to a total dose of 50-54 Gy based on tumor characteristics. Tempol gel will be applied to the bilateral groins and the gluteal cleft, avoiding a 3 cm radius from the anal verge, immediately prior to each fraction of RT. Radiation Therapy Oncology Group (RTOG) grading will be used to evaluate skin toxicity in both the groin and gluteal cleft weekly during treatment and at 4 weeks, 3 months and 6 months after completion of treatment. The duration of treatment, number of treatment breaks, opiate requirements, and level of pain will be evaluated weekly during treatment and at 4 weeks and 3 months after the completion of treatment. Disease control will be assessed at 4 weeks, 3 months, 6 months, 9 months, and 12 months of follow-up.

Conditions
Anal Cancer
Being tested
Tempol, 5-Fluorouracil, Mitomycin-C, Radiation Therapy
Keywords
Anal Cancer, Radioprotector, Topical, Radiation, Dermatitis
Medical subject headings
Anus Neoplasms, Dermatitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TempolDrug

    Also called MBM-02

    Tempol gel will be applied to the bilateral groins and the gluteal cleft, avoiding a 3 cm radius from the anal verge, immediately prior to each fraction of radiation therapy (RT).

  • 5-FluorouracilDrug

    Also called 5-FU

    5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29.

  • Mitomycin-CDrug

    Also called MMC

    Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29

  • Radiation TherapyProcedure or surgery

    Also called RT

    Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.

Study groups in NCT01324141
Study groupRoleWhat they receive
1/Chemo + RadiationExperimentalChemo + Radiation
Receives: Drug: Tempol; Drug: 5-Fluorouracil; Drug: Mitomycin-C; Procedure: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Grade 1 and Higher Adverse Events Possibly, Probably, or Definitely Related to Topical MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT)

    Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life threatening, and Grade 5 is death related to adverse event.

    Measured: Date treatment consent signed to date off study, approximately, 36 months and 10 days.

  2. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)

    Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Measured: Date treatment consent signed to date off study, approximately, 36 months and 10 days.

Secondary outcomes (19)

  1. Mean Grade of Toxicity at Each Timepoint and Location for All Participants Who Underwent Treatment

    RTOG grade 1-5 were used to assess skin toxicity in the groin (right and left inguinal area) and gluteal cleft, as well as two control sites. Grade 0 is no skin toxicity, Grade 1 is follicular, faint or dull erythema, Grade 3 is tender or bright erythema, Grade 3 is confluent, moist desquamation, Grade 4 is ulceration, hemorrhage, or necrosis, and Grade 5 is death due to radiation toxicity.

    Measured: baseline, weeks 1-6, follow up at 1 week, follow up at 2 weeks, and follow up at 4 weeks

  2. Number of Participants That Required a Treatment Break Relative to Hematologic Toxicity (Non-dermatologic)

    Number of participants that required a treatment break relative to hematologic (e.g. thrombocytopenia, leukopenia) toxicity (non-dermatologic).

    Measured: From beginning until completion of radiation treatment up to 46 days

  3. Number of Participants Treated With Topical MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT) That Required Opiates

    Opiates are strong drugs prescribed by prescription used for maximum pain relief.

    Measured: Completion of study, approximately 14 months after start of treatment

  4. Number of Participants With 12-month Progression-free Survival Treated With 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT)

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions.

    Measured: 12 months

  5. Change in the Levels of Number of Human Immunodeficiency Virus (HIV) in the Circulation Pre and Post Treatment

    Change in the levels of number of Human Immunodeficiency Virus (HIV) in the circulation pre and post treatment

    Measured: Completion of study, approximately 14 months

  6. Ratio of the Number of Cluster of Differentiation 4 (CD4): Cluster of Differentiation 8 (CD8) Cells in the Circulation and Tissue Pre and Post Treatment

    Ratio of the number Cluster of Differentiation 4 (CD4): Cluster of Differentiation 8 (CD8) cells in the circulation and tissue pre and post treatment. The number of cells of CD4 are divided by the number of cells of CD8.

    Measured: Pre-treatment and post treatment tissue (CD4), and pre-treatment and post treatment circulation (CD8)

  7. Number of Participants With 12 Month Disease Free Survival (DFS) Treated With 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT)

    DFS is defined as the duration of time from start of treatment to time of progression. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions.

    Measured: 12 months

  8. Overall Survival

    OS is defined as the duration of time from start of treatment to time of death.

    Measured: start of treatment to time of death, approximately 14 months

  9. Peripheral Blood Mononuclear Cells (Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor Alpha (TNF-alpha), Interleukin-7 (IL-7), and Transforming Growth Factor Beta-1 (TGF-beta1) Cell Counts at Baseline and Course 1 Day 28

    Peripheral blood mononuclear cells (Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-7 (IL-7), and Transforming Growth Factor beta-1 (TGF-beta1) were sampled from peripheral blood from rectal associated lymphoid tissue to evaluate immune cell subsets at baseline and after treatment with MTS-0 and 15-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT). It is unknown if a lower or higher numbers has prognostic significance.

    Measured: Baseline and Course 1 Day 28

  10. Number of Participants With Tumor Tissue Negative for Human Papilloma Virus (HPV)

    HPV is a sexually transmitted infection that can cause warts and cervical cancer. HPV test detects deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) of HPV in a cell sample (i.e. cervical).

    Measured: Pretreatment

  11. Brief Pain Inventory Score

    The Brief Pain Inventory Scale is a questionnaire that asks the participant to rate their pain on a scale of 0 (no pain) to 10 (worst pain).

    Measured: Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up

  12. Pain Interference

    The Brief Pain Inventory Scale questionnaire were used to assess pain interference. Participants rated pain interference on a scale of 0 (does not interfere) to 10 (completely interferes).

    Measured: Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up

  13. Mean Percentage Pain Relief After Medication

    The Brief Pain Inventory Scale questionnaire were used to assess pain relief after medication. Participants rated pain relief on a scale of 0% (no relief) to 100% (complete relief) and a mean and full range were reported.

    Measured: Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up

  14. Duration of Overall Response (DOR)

    Duration of overall response is measured from the time measurement criteria are met for Complete Response until the first date that recurrent or progressive disease is objectively document. Complete Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Complete Response is disappearance of all target lesions.

    Measured: 12 months of follow up, approximately 14 months

  15. Percentage of Total Viable Cells That Were Cluster of Differentiation 3+ (CD3+) Cells in Biopsied Tissue

    Percentage of total viable cells that were Cluster of differentiation 3+ (CD3+) cells in biopsied tissue.

    Measured: Baseline and 1 year

  16. Absolute Number of Cluster of Differentiation 3+ (CD3) Cells Per Gram of Biopsied Intestinal Tissue

    Absolute number of Cluster of differentiation 3+ (CD3) cells per gram of biopsied intestinal tissue. The number of CD3 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.

    Measured: Baseline and 1 year follow up

  17. Number of Cluster of Differentiation 8+ (CD8) Cells Per Gram of Biopsied Intestinal Tissue

    Number of Cluster of differentiation 8+ (CD8) cells per gram of biopsied intestinal tissue. The number of CD8 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.

    Measured: Baseline and 1 year follow up

  18. Number of Cluster of Differentiation 4+ (CD4) Cells Per Gram of Biopsied Intestinal Tissue

    Number of Cluster of Differentiation 4+ (CD4) cells per gram of biopsied intestinal tissue. The number of CD4 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.

    Measured: Baseline and 1 year follow up

  19. Number of Participants With Human Immunodeficiency Virus (HIV) in Biopsy Tissue From Rectal Mucosa

    Optional snag biopsies pre and post were collected from participants rectal mucosa to enumerate cell counts.

    Measured: Baseline and Course 1 Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2011 (estimated)
  2. Study start18 Mar 2011
  3. Primary completion15 Apr 2015
  4. Study completion15 Apr 2015

Why it stopped: Slow, insufficient accrual and failure to meet endpoints.

Resources

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
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01324141
Sponsor's protocol ID
110129
Other IDs
11-C-0129
Status last verified
Oct 2021
First submitted
25 Mar 2011
Last updated
23 Nov 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.

    PubMed 19474385

  • Bower M, Powles T, Newsom-Davis T, Thirlwell C, Stebbing J, Mandalia S, Nelson M, Gazzard B. HIV-associated anal cancer: has highly active antiretroviral therapy reduced the incidence or improved the outcome? J Acquir Immune Defic Syndr. 2004 Dec 15;37(5):1563-5. doi: 10.1097/00126334-200412150-00004.

    PubMed 15577408

  • Crum-Cianflone NF, Hullsiek KH, Marconi VC, Ganesan A, Weintrob A, Barthel RV, Agan BK; Infectious Disease Clinical Research Program HIV Working Group. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. AIDS. 2010 Feb 20;24(4):535-43. doi: 10.1097/QAD.0b013e328331f6e2.

    PubMed 19926961

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tempol, 5-Fluorouracil and Mitomycin-C in people with Anal Cancer, run by National Cancer Institute (NCI) 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 15 inclusion and 10 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: stopped early, as of the sponsor's last update on 23 Nov 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 23 Nov 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?

Number of Grade 1 and Higher Adverse Events Possibly, Probably, or Definitely Related to Topical MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT) (time frame: Date treatment consent signed to date off study, approximately, 36 months and 10 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01324141, which also lists 3 linked publications.

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 23 Nov 2021.

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