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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Compliance rates
Secondary Outcome
Acute GI and urinary toxicity
Condition
Endometrial Cancer
Intervention
carboplatin and paclitaxel
Study Arms / Comparison Groups
Concurrent chemoradiation
Description: Concurrent carboplatin and paclitaxel and IMPT (Intensity Modulated Proton Therapy)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
21
Start Date
November 1, 2020
Completion Date
September 1, 2024
Primary Completion Date
September 1, 2023
Eligibility Criteria
Inclusion Criteria:
1. Surgery must have included a hysterectomy. Bilateral salpingo-oophorectomy, pelvic
lymph node sampling, para-aortic lymph node sampling, and omentectomy are optional
2. Patients will be staged according to FIGO 2009 staging system. Eligibility is defined
based on clinical-pathologic features.
3. 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.
4. 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.
5. Patients with a GOG Performance Status of 0, 1, or 2
6. 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)
7. Patients who have signed an approved informed consent and authorization permitting
release of personal health information
8. Patients must be 18 years of age or older
Exclusion Criteria:
1. Patients with leiomyosarcoma
2. 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
3. Patients with recurrent endometrial cancer with gross nodal or vaginal disease
requiring high dose radiotherapy, or history of prior chemotherapy
4. 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.
5. Patients with a history of serious co-morbid illness or uncontrolled illnesses that
would preclude protocol therapy
6. Patients with an estimated survival of less than three months
7. Patients with FIGO 2009 Stage IVB endometrial cancer
8. Patients with a history of myocardial infarction, unstable angina, or uncontrolled
arrhythmia within 3 months from enrollment
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Pranshu Mohindra, MD, 410-328-6080, [email protected]
Administrative Informations
NCT ID
NCT04527900
Organization ID
HP-00092397
Responsible Party
Principal Investigator
Study Sponsor
University of Maryland, Baltimore
Study Sponsor
Pranshu Mohindra, MD, Principal Investigator, University of Maryland/Maryland Proton Treatment Center
Verification Date
September 2020