Comparison of Proton or Intensity Modulated Radiation Therapy After Surgery for Endometrial or Cervical Cancer

A Comparison of Acute Toxicities Between Patients Treated With Protons or Intensity-Modulated Radiation Therapy for Post-Operative Treatment of Endometrial or Cervical Cancers

This early phase I trial compares the side effects between patients treated with proton radiation therapy versus intensity modulated radiation therapy after surgery for the treatment of endometrial or cervical cancer. Radiation therapy uses high energy protons or x-rays to kill tumor cells and shrink tumors. Using quality of life questionnaires and adverse event assessments may help doctors learn whether proton radiation therapy is associated with lower acute gastrointestinal toxicities at the end of treatment compared to intensity modulated radiation therapy in patients with endometrial or cervical cancer.

Study Overview

• Status: Recruiting
• Conditions: Endometriosis; Cervical Carcinoma; Endometrial Carcinoma; Pelvic Inflammatory Disease
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy

Detailed Description

PRIMARY OBJECTIVE:

I. To assess whether proton radiation therapy (RT) is associated with lower acute gastrointestinal toxicities at the end of treatment compared to intensity modulated radiation therapy (IMRT) as measured with the Expanded Prostate Cancer Index Composite (EPIC) bowel domain.

SECONDARY OBJECTIVES:

I. To examine the association of bowel and bladder dose-volume histogram (DVH) with bowel and bladder toxicities, respectively.

II. To assess whether urinary toxicity rate is improved with proton RT compared to IMRT as measured with the EPIC urinary domain.

III. To determine if well-being is improved with proton RT compared to IMRT as measured by the Functional Assessment of Cancer Therapy (FACT) cervix domain.

IV. To determine if proton RT reduces grade 2+ hematologic toxicities (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4.0) compared to IMRT.

V. Evaluate progression-free and overall survival between patients receiving proton RT and IMRT.

VI. To determine if proton RT improves overall patient quality of life compared to IMRT using the European Quality of Life Five Dimension (EQ-5D) questionnaire.

EXPLORATORY OBJECTIVES:

I. Evaluate ability to tolerate chemotherapy concurrent or after RT. II. Correlate bone marrow DVH with blood marrow function, and ability to tolerate chemotherapy concurrently or after RT.

III. Correlate bowel and skin DVH with acute toxicity. IV. To evaluate patient-reported gastrointestinal (GI) toxicities as a predictor of assigned treatment regimen, as well as physician-reported GI toxicities as a predictor of assigned treatment regimen.

V. Confirm the validity of the EPIC bowel and urinary domains when referencing the last 7 days.

OUTLINE:

Patients undergo standard of care proton or intensity modulated radiation therapy. Patients also complete quality of life questionnaires and adverse event assessments over 10-15 minutes each at baseline, at the end of radiation therapy, and at 1 month, 1 year, and 3 years post-radiation therapy.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic in Arizona
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Sujay A. Vora, M.D.
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Daniel M. Trifiletti, M.D.
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Clinical Trials Referra Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Allison E. Garda, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of cervical or endometrial cancer
• Must have undergone an open or robotic hysterectomy (total abdominal, vaginal, radical, or total laparoscopic) for carcinoma of the cervix or endometrium
• History and physical prior to registration

• Documentation of history of:

  • Smoking status
  • Pelvic infection
  • Pelvic inflammatory disease
  • Endometriosis
• Planned to receive either proton or IMRT radiation treatment, with use of rectal balloon, at an Institutional Review Board (IRB)-approved Mayo Clinic site
• Plan for RT to pelvis with or without para-aortic lymph node irradiation
• If received high-dose chemotherapy prior to registration, last dose must have been given >= 21 days prior to start of RT
• Complete blood count (CBC) performed within 21 days prior to registration
• Computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, or PET/MRI for staging before registration; may be pre-operative (op) or post-op
• Eastern Cooperative Oncology Group (ECOG) performance score 0-2
• Provide written informed consent
• Willing to complete quality of life (QOL) questionnaires

Exclusion Criteria:

• Receiving external beam boost dose during RT
• Distant metastases
• Gross disease at time of RT
• Histology of endometrial stromal sarcoma, leiomyosarcoma, melanoma or small cell carcinomas
• Patients who exceed the weight/size limits of the treatment table
• Positive or close surgical margins (=< 3 mm)
• Prior RT to the pelvis
• Planned to receive inguinal node RT
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be immunosuppressive.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years

• 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
• Other major medical illness which requires hospitalization or precludes study therapy at the time of registration
• Patients unwilling to have rectal balloon placed on a daily basis during RT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (radiation therapy, questionnaires); Patients undergo standard of care proton or intensity modulated radiation therapy. Patients also complete quality of life questionnaires and adverse event assessments over 10-15 minutes each at baseline, at the end of radiation therapy, and at 1 month, 1 year, and 3 years post-radiation therapy.

Other: Quality-of-Life Assessment; Complete quality of life questionnaires; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Complete adverse event assessments; Radiation: Radiation Therapy; Undergo proton or intensity modulated radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Expanded Prostate Cancer Index Composite (EPIC) Bowel score	Will be examined using analysis of covariance.	Baseline up to 3 years post-radiation therapy (RT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bowel and bladder dose-volume histogram (DVH) parameters	Will be examined in association with the change in EPIC Bowel and Urinary scores using analysis of covariance, considering the DVH variables as model covariates.	Up to 3 years post-RT
Change in EPIC Urinary score	Will be examined using analysis of covariance.	Baseline up to 5 weeks
Well-being	Measured by the Functional Assessment of Cancer Therapy cervix domain. Will be examined using analysis of covariance.	Up to 3 years post-RT
Incidence of grade 2+ hematologic toxicities	Measured by Common Terminology Criteria for Adverse Events version 4.0. Will be examined using logistic regression.	Up to 3 years post-RT
Progression-free survival	Will be examined using survival methods. Cumulative probability of progression rates will be calculated treating death as a competing risk. Cox models will be used to assess the association of treatment received (proton RT versus intensity modulated radiation therapy [IMRT]).	Up to 3 years post-RT
Overall survival (OS)	Will be examined using survival methods. Estimates of OS will be calculated using the Kaplan Meier method. Cox models will be used to assess the association of treatment received (proton RT versus IMRT).	Up to 3 years post-RT
Change in overall patient quality of life	Measured by the European Quality of Life Five Dimension Five Level Scale Questionnaire. Will be examined using analysis of covariance.	Baseline up to 3 years post-RT

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Allison E. Garda, M.D., Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2020
• Primary Completion (Estimated): October 15, 2024
• Study Completion (Estimated): October 15, 2024

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Adnexal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma; Endometriosis; Endometrial Neoplasms; Pelvic Inflammatory Disease; Pelvic Infection
• Other Study ID Numbers: ROR1904 (Other Identifier: Mayo Clinic Radiation Oncology); NCI-2020-06936 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 19-004792 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No