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The UPPROACH (Upfront Intensity Modulated Proton Beam Therapy) Approach

Primary Purpose

Endometrial Cancer

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

carboplatin and paclitaxel

pelvic IMPT (Intensity Modulated Proton Therapy)

About this trial

This is an interventional treatment trial for Endometrial Cancer focused on measuring Endometrial cancer, Gynecologic cancers, Radiotherapy, Proton Therapy, Chemotherapy, Chemoradiation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Surgery must have included a hysterectomy. Bilateral salpingo-oophorectomy, pelvic lymph node sampling, para-aortic lymph node sampling, and omentectomy are optional
Patients will be staged according to FIGO 2009 staging system. Eligibility is defined based on clinical-pathologic features.
Patients with endometrioid endometrial cancer with the following:
- Stage IA grade 3 with extensive LVSI
- Stage IB grade 3
- Stage II
- Stage III (A, B, and C)
- Stage IVA who are recommended adjuvant whole pelvic RT (+/- lower para-aortic up to renal hilum) and systemic chemotherapy.
Patients with clear cell, serous papillary carcinoma, or carcinosarcoma with stages IA-III who are recommended adjuvant whole pelvic RT (+/- lower para-aortic up to renal hilum) and systemic chemotherapy.
Patients with a GOG Performance Status of 0, 1, or 2
Patients with adequate organ function, reflected by the following parameters:
- WBC ≥ 3000/mcl
- Absolute neutrophil count (ANC) ≥ 1000/mcl
- Platelet count ≥ 100,000/mcl
- SGOT, SGPT, and alkaline phosphatase ≤ 2.5 X upper limit of normal (ULN)
- Bilirubin ≤ 1.5 X ULN
- Creatinine ≤ institutional ULN (if serum creatinine > ULN, estimated GFR ≥ 45 ml/min)
Patients who have signed an approved informed consent and authorization permitting release of personal health information
Patients must be 18 years of age or older

Exclusion Criteria:

Patients with leiomyosarcoma
Patients with clinically significant pelvic or para-aortic nodal disease, on post-surgery CT scan, that was not dissected and would require higher boost dose
Patients with recurrent endometrial cancer with gross nodal or vaginal disease requiring high dose radiotherapy, or history of prior chemotherapy
Patients with a history of prior pelvic/abdominal RT or with history of prior cancer treatment that contraindicates this protocol therapy including history of prior chemotherapy for any other malignancy.
Patients with a history of serious co-morbid illness or uncontrolled illnesses that would preclude protocol therapy
Patients with an estimated survival of less than three months
Patients with FIGO 2009 Stage IVB endometrial cancer
Patients with a history of myocardial infarction, unstable angina, or uncontrolled arrhythmia within 3 months from enrollment

Sites / Locations

Maryland Proton Treatment CenterRecruiting
UMMCRecruiting
Central Maryland Radiation OncologyRecruiting
Baltimore Washington Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Concurrent chemoradiation

Arm Description

Concurrent carboplatin and paclitaxel and IMPT (Intensity Modulated Proton Therapy)

Outcomes

Primary Outcome Measures

Compliance rates

This will be measured as proportion of patients completing full 6 cycles of chemotherapy concurrently with IMPT

Secondary Outcome Measures

Acute GI and urinary toxicity

Measured by CTCAE (Common Terminology Criteria for Adverse Events)

Acute GI and urinary toxicity

Measured by PRO-CTCAE (Patient reported outcomes Common Terminology Criteria for Adverse Events)

Acute GI and urinary toxicity

Measured by EPIC (Expanded Prostate Cancer Index Composite ) bowel and urinary domain

Acute hematologic toxicity

Measured by CTCAE (Common Terminology Criteria for Adverse Events)

Late GI and urinary toxicity

Measured by CTCAE (Common Terminology Criteria for Adverse Events)

Late GI and urinary toxicity

Measured by PRO-CTCAE (Patient reported outcomes Common Terminology Criteria for Adverse Events)

Late GI and urinary toxicity

Measured by EPIC (Expanded Prostate Cancer Index Composite ) bowel and urinary domain

Full Information

NCT ID

NCT04527900

First Posted

August 14, 2020

Last Updated

May 2, 2023

Sponsor

University of Maryland, Baltimore

1. Study Identification

Unique Protocol Identification Number

NCT04527900

Brief Title

The UPPROACH (Upfront Intensity Modulated Proton Beam Therapy) Approach

Official Title

The "Upproach" Approach: A Phase 2 Study Of Upfront Intensity Modulated Proton Beam Therapy (Impt) And Concurrent Chemotherapy For Post-Operative Treatment In Loco-Regionally Advanced Endometrial Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 23, 2021 (Actual)

Primary Completion Date

September 1, 2025 (Anticipated)

Study Completion Date

September 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

A phase 2 study with the primary objective of testing treatment compliance of Upfront Intensity Modulated Proton Beam Therapy (IMPT) and Concurrent Chemotherapy (UPPROACH) for Post-operative Treatment in Loco-regionally Advanced Endometrial Cancer is non-inferior to the historic compliance rate of the chemoradiation arm of GOG 258 study

Detailed Description

While there is a consensus that both adjuvant ChT and RT benefit patients with respect to locoregional and distant control, the sequencing of these therapies varies between institutions. Common approaches include sequential treatment, with 4-6 cycles of ChT followed by RT, sandwich therapy with RT sandwiched between 3 cycles of ChT, or concurrent CRT. Small retrospective studies have shown a benefit with respect to PFS and OS in the sandwich approach, however this has not been replicated in larger studies. In more recent years, proton beam therapy (PBT) has become an increasingly common modality for the treatment of uterine malignancies and is capable of even more precise dose distributions than photon-based RT due to intrinsic properties of these much heavier particles. Dosimetric/planning studies from other institutions confirm the significant reduction of dose to critical normal tissues like bladder, bowel, rectum, and bone marrow. Preliminary data from the University of Maryland Medical Center has suggested that IMPT using pencil beam scanning is feasible in patients with endometrial cancer, with only 10% of patients developing grade 2 GI toxicity and no patients developing ≥ grade 3 GI or GU toxicities (abstract under review). The investigators would like to test the hypothesis that in the postoperative setting, patients with advanced endometrial cancer will be able to complete a course of full dose ChT - carboplatin and paclitaxel - concurrent with upfront pelvic IMPT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endometrial Cancer

Keywords

Endometrial cancer, Gynecologic cancers, Radiotherapy, Proton Therapy, Chemotherapy, Chemoradiation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Concurrent chemoradiation

Arm Type

Experimental

Arm Description

Concurrent carboplatin and paclitaxel and IMPT (Intensity Modulated Proton Therapy)

Intervention Type

Drug

Intervention Name(s)

carboplatin and paclitaxel

Intervention Description

carboplatin and paclitaxel 5-6 cycles (dosage per standard of care according to treating oncologist)

Intervention Type

Radiation

Intervention Name(s)

pelvic IMPT (Intensity Modulated Proton Therapy)

Intervention Description

whole pelvis will receive a total dose of 4500 cGy in 25 fractions to 5040 cGy in 28 fractions

Primary Outcome Measure Information:

Title

Compliance rates

Description

This will be measured as proportion of patients completing full 6 cycles of chemotherapy concurrently with IMPT

Time Frame

End of study, approximately 4 years

Secondary Outcome Measure Information:

Title

Acute GI and urinary toxicity

Description

Measured by CTCAE (Common Terminology Criteria for Adverse Events)

Time Frame

once a week during radiation treatment (5-6 weeks)

Title

Acute GI and urinary toxicity

Description

Measured by PRO-CTCAE (Patient reported outcomes Common Terminology Criteria for Adverse Events)

Time Frame

once a week during radiation treatment (5-6 weeks)

Title

Acute GI and urinary toxicity

Description

Measured by EPIC (Expanded Prostate Cancer Index Composite ) bowel and urinary domain

Time Frame

once a week during radiation treatment (5-6 weeks)

Title

Acute hematologic toxicity

Description

Measured by CTCAE (Common Terminology Criteria for Adverse Events)

Time Frame

Prior to each cycle of chemotherapy (once every 21 days for 106 days)

Title

Late GI and urinary toxicity

Description

Measured by CTCAE (Common Terminology Criteria for Adverse Events)

Time Frame

6-month following radiation therapy

Title

Late GI and urinary toxicity

Description

Measured by PRO-CTCAE (Patient reported outcomes Common Terminology Criteria for Adverse Events)

Time Frame

6-month following radiation therapy

Title

Late GI and urinary toxicity

Description

Measured by EPIC (Expanded Prostate Cancer Index Composite ) bowel and urinary domain

Time Frame

6-month following radiation therapy

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Surgery must have included a hysterectomy. Bilateral salpingo-oophorectomy, pelvic lymph node sampling, para-aortic lymph node sampling, and omentectomy are optional Patients will be staged according to FIGO 2009 staging system. Eligibility is defined based on clinical-pathologic features. Patients with endometrioid endometrial cancer with the following: Stage IA grade 3 with extensive LVSI Stage IB grade 3 Stage II Stage III (A, B, and C) Stage IVA who are recommended adjuvant whole pelvic RT (+/- lower para-aortic up to renal hilum) and systemic chemotherapy. Patients with clear cell, serous papillary carcinoma, or carcinosarcoma with stages IA-III who are recommended adjuvant whole pelvic RT (+/- lower para-aortic up to renal hilum) and systemic chemotherapy. Patients with a GOG Performance Status of 0, 1, or 2 Patients with adequate organ function, reflected by the following parameters: WBC ≥ 3000/mcl Absolute neutrophil count (ANC) ≥ 1000/mcl Platelet count ≥ 100,000/mcl SGOT, SGPT, and alkaline phosphatase ≤ 2.5 X upper limit of normal (ULN) Bilirubin ≤ 1.5 X ULN Creatinine ≤ institutional ULN (if serum creatinine > ULN, estimated GFR ≥ 45 ml/min) Patients who have signed an approved informed consent and authorization permitting release of personal health information Patients must be 18 years of age or older Exclusion Criteria: Patients with leiomyosarcoma Patients with clinically significant pelvic or para-aortic nodal disease, on post-surgery CT scan, that was not dissected and would require higher boost dose Patients with recurrent endometrial cancer with gross nodal or vaginal disease requiring high dose radiotherapy, or history of prior chemotherapy Patients with a history of prior pelvic/abdominal RT or with history of prior cancer treatment that contraindicates this protocol therapy including history of prior chemotherapy for any other malignancy. Patients with a history of serious co-morbid illness or uncontrolled illnesses that would preclude protocol therapy Patients with an estimated survival of less than three months Patients with FIGO 2009 Stage IVB endometrial cancer Patients with a history of myocardial infarction, unstable angina, or uncontrolled arrhythmia within 3 months from enrollment

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Pranshu Mohindra, MD

Phone

410-328-6080

pmohindra@umm.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Ermiece Straub, MS

Phone

410-328-8018

ermiece.straub@umm.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pranshu Mohindra, MD

Organizational Affiliation

University of Maryland/Maryland Proton Treatment Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Maryland Proton Treatment Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ermiece Straub

Phone

410-328-8018

ermiece.straub@umm.edu

Facility Name

UMMC

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ermiece Straub

Phone

410-328-8018

ermiece.straub@umm.edu

Facility Name

Central Maryland Radiation Oncology

City

Columbia

State/Province

Maryland

ZIP/Postal Code

21044

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ermiece Straub

Phone

410-328-8018

ermiece.straub@umm.edu

Facility Name

Baltimore Washington Medical Center

City

Glen Burnie

State/Province

Maryland

ZIP/Postal Code

21061

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pilar Strycula

P.Strycula@umm.edu

12. IPD Sharing Statement

Learn more about this trial

The UPPROACH (Upfront Intensity Modulated Proton Beam Therapy) Approach

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