Comparison of Acute Toxicities Between Patients Treated With Protons or Intensity Modulated Radiation Therapy After Surgery for the Treatment of Endometrial or Cervical Cancer

• ClinicalTrials.gov Identifier: NCT04567771
• Recruitment Status: Recruiting
• First Posted: September 28, 2020
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cervical Carcinoma; Endometrial Carcinoma; Endometriosis; Pelvic Inflammatory Disease	Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Comparison of Acute Toxicities Between Patients Treated With Protons or Intensity-Modulated Radiation Therapy for Post-Operative Treatment of Endometrial or Cervical Cancers
• Actual Study Start Date: December 4, 2020
• Estimated Primary Completion Date: October 15, 2023
• Estimated Study Completion Date: October 15, 2024

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Bowel and bladder dose-volume histogram (DVH) parameters [ Time Frame: Up to 3 years post-RT ]
   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.
2. Change in EPIC Urinary score [ Time Frame: Baseline up to 5 weeks ]
   Will be examined using analysis of covariance.
3. Well-being [ Time Frame: Up to 3 years post-RT ]
   Measured by the Functional Assessment of Cancer Therapy cervix domain. Will be examined using analysis of covariance.
4. Incidence of grade 2+ hematologic toxicities [ Time Frame: Up to 3 years post-RT ]
   Measured by Common Terminology Criteria for Adverse Events version 4.0. Will be examined using logistic regression.
5. Progression-free survival [ Time Frame: Up to 3 years post-RT ]
   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]).
6. Overall survival (OS) [ Time Frame: Up to 3 years post-RT ]
   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).
7. Change in overall patient quality of life [ Time Frame: Baseline up to 3 years post-RT ]
   Measured by the European Quality of Life Five Dimension Five Level Scale Questionnaire. Will be examined using analysis of covariance.

Eligibility Criteria

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

Criteria

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
• Patients with active and/or inflammatory irritable bowel disease
• 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

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic in Arizona; Recruiting

Scottsdale, Arizona, United States, 85259

Contact: Clinical Trials Referral Office 855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator: Sujay A. Vora, M.D.

United States, Florida

Mayo Clinic in Florida; Recruiting

Jacksonville, Florida, United States, 32224-9980

Contact: Clinical Trials Referral Office 855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator: Katherine S. Tzou, M.D.

United States, Minnesota

Mayo Clinic in Rochester; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Clinical Trials Referra Office 855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator: Ivy A. Petersen, M.D.

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ivy A Petersen; Mayo Clinic in Rochester

More Information

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04567771
• Other Study ID Numbers: ROR1904; NCI-2020-06936 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); ROR1904 ( Other Identifier: Mayo Clinic in Rochester ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Posted: September 28, 2020
• Last Update Posted: June 11, 2021
• Last Verified: June 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Pelvic Inflammatory Disease; Pelvic Infection; Carcinoma; Uterine Cervical Neoplasms; Endometrial Neoplasms; Endometriosis; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Infection; Adnexal Diseases