Anal Canal Squamous Cell CarcinomaPhase 2NCT03690921
Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT) as a Component of Definitive Chemoradiation for Newly Diagnosed Squamous Cell Carcinoma of the Anal Canal: a Feasibility Trial
A Phase 2 study testing Cisplatin, Fluorouracil and Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy in people with Anal Canal Squamous Cell Carcinoma and Stage I Anal Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies the side effects of LET-IMPT and standard chemotherapy, and how well they work in treating patients with newly diagnosed stage I-III anal canal squamous cell cancer. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Anal Canal Squamous Cell Carcinoma, Stage I Anal Cancer AJCC v8, Stage II Anal Cancer AJCC v8
- What is being tested?
- Cisplatin, Fluorouracil and Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2018to 3 Jun 2022
- Phase
- Phase 2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically-proven, non-metastatic invasive primary squamous cell carcinoma of the anal canal (stages I, II, and III)
- History/physical examination including documentation of the primary anal lesion size, distance from the anal verge and anal sphincter tone within 60 days prior to registration
- Anal examination with biopsy on either colonoscopy, sigmoidoscopy, rigid proctoscopy or anoscopy
- Computed tomography (CT) scan of the chest and abdomen with contrast or contrast-enhanced positron emission tomography (PET)/CT scan within 60 days of registration unless the patient has a documented contrast allergy
- CT scan of pelvis with contrast or contrast-enhanced PET/CT scan within 60 days of registration unless the patient has a documented contrast allergy
- Zubrod performance status of 0-1 within 60 days prior to registration
Show all 18Show fewer
- Absolute neutrophil count (ANC) >=1.8 K/ul, cannot be achieved through granulocyte-colony stimulating factor (GCSF) (within 30 days prior to study registration)
- Platelets >= 100 K/uL, cannot be achieved through transfusion (within 30 days prior to study registration)
- Hemoglobin >= 8 g/dL, cannot be achieved through transfusion (within 30 days prior to study registration)
- Serum creatinine =< 1.5 mg/dL (within 30 days prior to study registration)
- Bilirubin =< 1.4 mg/dL, except in the case of patients with Gilbert's disease (within 30 days prior to study registration)
- White blood cells (WBC) >= 3000/microliter (within 30 days prior to study registration)
- Aspartate transaminase (AST)/alanine transaminase (ALT) < 3 x the upper limit of normal (within 30 days prior to study registration)
- International normalized ratio (INR) =< 1.5 (within 30 days prior to study registration)
- Human Immunodeficiency Virus (HIV) test must be done within 30 days of study registration. If HIV positive, CD4 count must be obtained within 30 days of study registration
- Note: HIV positive patients are eligible for this study if they have a CD4 count > 400 cells/mm^3
- The patient must either have insurance authorization or otherwise secure funding to cover IMPT
- The patient must be able to receive concurrent chemotherapy
Who cannot join
- Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years
- Prior systemic chemotherapy for anal cancer
- Prior radiotherapy to the pelvis that would result in overlap of radiation fields
- Evidence of distant metastatic disease (M1)
- Prior surgery to the anal canal that removed all macroscopic anal cancer
- Women of childbearing potential or men who do not agree to use a medically effective form of birth control throughout their participation in the treatment phase of the study
- Severe, active co-morbidity defined as follows: unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; transmural myocardial infarction within the last 6 months; acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; HIV positive with a CD4 count < 400 cells/mm^3; other immuno-compromised status; women who are pregnant or lactating; uncontrolled infection as deemed by the principal investigator (PI); patient incarceration
Trial locations and contacts
1 site in 1 country.
About this study
This phase II trial studies the side effects of LET-IMPT and standard chemotherapy, and how well they work in treating patients with newly diagnosed stage I-III anal canal squamous cell cancer. LET-IMPT is a type of radiation therapy that uses high energy proton "beamlets" to "paint" the radiation dose into the target and may help to kill tumor cells and shrink tumors. Giving LET-IMPT and standard chemotherapy may work better in treating patients with anal canal squamous cell cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess physician-reported acute grade 3 or greater gastrointestinal, genitourinary and hematologic toxicities at 12 weeks post-treatment for patients treated with linear energy transfer (LET)-optimized, intensity-modulated proton therapy (IMPT) and compare to contemporary controls treated with volume modulated arc therapy (VMAT) to determine the feasibility of this outcome for a future randomized trial.
SECONDARY OBJECTIVES:
- To assess the feasibility of enrolling patients on a prospective trial delivering LET-optimized IMPT for newly diagnosed, non-metastatic anal cancer.
II. To develop guidelines and workflow to create and deliver anal canal cancer treatments using LET-optimized IMPT.
III. To evaluate complete response rate at 12 weeks and 24 weeks post-treatment.
IV. To evaluate local progression free survival, distant metastasis-free survival and overall survival at 24 and 48 months.
- To evaluate rates of patient-reported acute toxicity, function, distress and quality of life (QOL) at 12 weeks.
VI. To evaluate rates of patient-reported late toxicity, function, distress and QOL every 6 months for 24 months.
VII. To evaluate the value of proton therapy by comparing Time-Driven Activity-Based Costing data from the date of consultation until the date of the 12-week follow up visit post-treatment with contemporary controls treated with VMAT.
EXPLORATORY OBJECTIVES:
- To compare dose to the pelvic bone marrow, bowel, bladder and genitalia between LET-optimized IMPT, traditionally-optimized IMPT and VMAT.
II. To assess rates of leukopenia, neutropenia and lymphopenia at 12-weeks post-treatment for patients treated with LET-optimized IMPT and compare to contemporary controls treated with VMAT.
III. To correlate white blood cell counts (WBC), absolute neutrophil counts (ANC) and absolute lymphocyte counts (ALC) with dose to the pelvic bone marrow for patients treated with LET-optimized IMPT.
OUTLINE:
Patients undergo linear energy transfer-optimized intensity modulated proton therapy 5 times per week for 5-6 weeks. Patients also receive standard cisplatin and fluorouracil intravenously (IV) weekly for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 12 weeks.
- Conditions
- Anal Canal Squamous Cell Carcinoma, Stage I Anal Cancer AJCC v8, Stage II Anal Cancer AJCC v8, Stage IIA Anal Cancer AJCC v8, Stage IIB Anal Cancer AJCC v8, Stage III Anal Cancer AJCC v8
- Being tested
- Cisplatin, Fluorouracil, Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy, Quality-of-Life Assessment, Questionnaire Administration
- Medical subject headings
- Anus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Also called Abiplatin, Blastolem, Briplatin, CDDP
Given IV
FluorouracilDrug
Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Given IV
Linear Energy Transfer-Optimized Intensity Modulated Proton TherapyRadiation
Also called LET-Optimized IMPT, LET-Optimized Intensity Modulated Proton Therapy, Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT)
Undergo LET-IMPT
Quality-of-Life AssessmentProcedure or surgery
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (LET-IMPT, chemotherapy) | Experimental | Patients undergo linear energy transfer-optimized intensity modulated proton therapy 5 times per week for 5-6 weeks. Patients also receive standard cisplatin and fluorouracil IV weekly for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cisplatin; Drug: Fluorouracil; Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy; Procedure: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Toxicity
Number (percentage) of patients with physician-reported acute G3+ GI, GU and heme toxicities
Measured: Acute physician reported toxicity from start of treatment 12 weeks post-treatment
Secondary outcomes (5)
Complete Response at 12 Weeks
Number (percentage) patients who achieved a complete clinical response of their disease by 12 weeks after chemoradiation.
Measured: 12 weeks
Local Progression Free Survival at 24 Months
Patients alive without evidence of local progression 24 months after chemoradiation.
Measured: 24 months
Distant Metastasis-free Survival at 24 Months.
Patients alive without evidence of distant metastases 24 months after chemoradiation.
Measured: 24 months
Overall Survival at 24 Months
Patients alive 24 months after chemoradiation.
Measured: 24 months
Complete Response at 24 Weeks
Number (percentage) patients who achieved a complete clinical response of their disease by 24 weeks after chemoradiation.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2018
- Study start8 Nov 2018
- Primary completion3 Jun 2022
- Study completion3 Jun 2022
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 Anal Canal Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Emma B Holliday, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03690921
- Sponsor's protocol ID
- 2018-0420
- Other IDs
- NCI-2018-02040, 2018-0420
- Status last verified
- Jun 2023
- First submitted
- 27 Sep 2018
- Last updated
- 29 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT) as a Component of Definitive Chemoradiation for Newly Diagnosed Squamous Cell Carcinoma of the Anal Canal: a Feasibility Trial
- ClinicalTrials.gov ID
- NCT03690921
- Acronym / sponsor ID
- 2018-0420
- Conditions
- Anal Canal Squamous Cell Carcinoma, Stage I Anal Cancer AJCC v8, Stage II Anal Cancer AJCC v8, Stage IIA Anal Cancer AJCC v8, Stage IIB Anal Cancer AJCC v8, Stage III Anal Cancer AJCC v8
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 8 Nov 2018 (actual)
- Primary completion
- 3 Jun 2022 (actual)
- Study completion
- 3 Jun 2022 (actual)
- First posted
- 1 Oct 2018 (actual)
- Results
- Posted 29 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies the side effects of LET-IMPT and standard chemotherapy, and how well they work in treating patients with newly diagnosed stage I-III anal canal squamous cell cancer. LET-IMPT is a type of radiation therapy that uses high energy proton "beamlets" to "paint" the radiation dose into the target and may help to kill tumor cells and shrink tumors. Giving LET-IMPT and standard chemotherapy may work better in treating patients with anal canal squamous cell cancer.
Detailed description
PRIMARY OBJECTIVES:
- To assess physician-reported acute grade 3 or greater gastrointestinal, genitourinary and hematologic toxicities at 12 weeks post-treatment for patients treated with linear energy transfer (LET)-optimized, intensity-modulated proton therapy (IMPT) and compare to contemporary controls treated with volume modulated arc therapy (VMAT) to determine the feasibility of this outcome for a future randomized trial.
SECONDARY OBJECTIVES:
- To assess the feasibility of enrolling patients on a prospective trial delivering LET-optimized IMPT for newly diagnosed, non-metastatic anal cancer.
II. To develop guidelines and workflow to create and deliver anal canal cancer treatments using LET-optimized IMPT.
III. To evaluate complete response rate at 12 weeks and 24 weeks post-treatment.
IV. To evaluate local progression free survival, distant metastasis-free survival and overall survival at 24 and 48 months.
- To evaluate rates of patient-reported acute toxicity, function, distress and quality of life (QOL) at 12 weeks.
VI. To evaluate rates of patient-reported late toxicity, function, distress and QOL every 6 months for 24 months.
VII. To evaluate the value of proton therapy by comparing Time-Driven Activity-Based Costing data from the date of consultation until the date of the 12-week follow up visit post-treatment with contemporary controls treated with VMAT.
EXPLORATORY OBJECTIVES:
- To compare dose to the pelvic bone marrow, bowel, bladder and genitalia between LET-optimized IMPT, traditionally-optimized IMPT and VMAT.
II. To assess rates of leukopenia, neutropenia and lymphopenia at 12-weeks post-treatment for patients treated with LET-optimized IMPT and compare to contemporary controls treated with VMAT.
III. To correlate white blood cell counts (WBC), absolute neutrophil counts (ANC) and absolute lymphocyte counts (ALC) with dose to the pelvic bone marrow for patients treated with LET-optimized IMPT.
OUTLINE:
Patients undergo linear energy transfer-optimized intensity modulated proton therapy 5 times per week for 5-6 weeks. Patients also receive standard cisplatin and fluorouracil intravenously (IV) weekly for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 12 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (LET-IMPT, chemotherapy) | Experimental | Drug: Cisplatin, Drug: Fluorouracil, Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy, Procedure: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients undergo linear energy transfer-optimized intensity modulated proton therapy 5 times per week for 5-6 weeks. Patients also receive standard cisplatin and fluorouracil IV weekly for up to 6 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically-proven, non-metastatic invasive primary squamous cell carcinoma of the anal canal (stages I, II, and III)
- History/physical examination including documentation of the primary anal lesion size, distance from the anal verge and anal sphincter tone within 60 days prior to registration
- Anal examination with biopsy on either colonoscopy, sigmoidoscopy, rigid proctoscopy or anoscopy
- Computed tomography (CT) scan of the chest and abdomen with contrast or contrast-enhanced positron emission tomography (PET)/CT scan within 60 days of registration unless the patient has a documented contrast allergy
- CT scan of pelvis with contrast or contrast-enhanced PET/CT scan within 60 days of registration unless the patient has a documented contrast allergy
Key exclusion criteria (7 listed)
- Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years
- Prior systemic chemotherapy for anal cancer
- Prior radiotherapy to the pelvis that would result in overlap of radiation fields
- Evidence of distant metastatic disease (M1)
- Prior surgery to the anal canal that removed all macroscopic anal cancer
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 |
|---|---|---|
| CisplatinAlso: Abiplatin, Blastolem, Briplatin, CDDPGiven IV | Drug | Treatment (LET-IMPT, chemotherapy) |
| FluorouracilAlso: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedioneGiven IV | Drug | Treatment (LET-IMPT, chemotherapy) |
| Linear Energy Transfer-Optimized Intensity Modulated Proton TherapyAlso: LET-Optimized IMPT, LET-Optimized Intensity Modulated Proton Therapy, Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT)Undergo LET-IMPT | Radiation | Treatment (LET-IMPT, chemotherapy) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Procedure or surgery | Treatment (LET-IMPT, chemotherapy) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (LET-IMPT, chemotherapy) |
Primary outcome
Acute Toxicity
Time frame: Acute physician reported toxicity from start of treatment 12 weeks post-treatment
Number (percentage) of patients with physician-reported acute G3+ GI, GU and heme toxicities
5 secondary outcomes
Complete Response at 12 Weeks
Time frame: 12 weeks
Local Progression Free Survival at 24 Months
Time frame: 24 months
Distant Metastasis-free Survival at 24 Months.
Time frame: 24 months
Overall Survival at 24 Months
Time frame: 24 months
Complete Response at 24 Weeks
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer CenterLink provided by the sponsor.
Related trials for Anal Canal Squamous Cell Carcinoma
Active, not recruitingPhase 3
Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer
Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma
Active, not recruitingPhase 3
EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients
Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma
Active, not recruitingPhase 2
Lower-Dose Chemoradiation in Treating Patients With Early-Stage Anal Cancer, the DECREASE Study
Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma
RecruitingPhase 1
Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors
Head and Neck Squamous Cell Carcinoma, Squamous Cell Carcinoma of Anal Canal
Active, not recruitingPhase 2
Nivolumab With or Without Ipilimumab in Treating Patients With Refractory Metastatic Anal Canal Cancer
Anal Canal Squamous Cell Carcinoma, Metastatic Anal Canal Carcinoma
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.
Emma B Holliday principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cisplatin, Fluorouracil and Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy in people with Anal Canal Squamous Cell Carcinoma and Stage I Anal Cancer AJCC v8, run by M.D. Anderson Cancer 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 18 inclusion and 7 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 29 Jun 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 29 Jun 2023). 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?
Acute Toxicity (time frame: Acute physician reported toxicity from start of treatment 12 weeks post-treatment). 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 29 Jun 2023; AzTrials last refreshed its copy on 30 Oct 2026.