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Clinical Trials/NCT04527900
NCT04527900
Terminated
Phase 2

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

University of Maryland, Baltimore4 sites in 1 country2 target enrollmentFebruary 23, 2021

Overview

Phase
Phase 2
Intervention
pelvic IMPT (Intensity Modulated Proton Therapy)
Conditions
Endometrial Cancer
Sponsor
University of Maryland, Baltimore
Enrollment
2
Locations
4
Primary Endpoint
Compliance rates
Status
Terminated
Last Updated
10 months ago

Overview

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.

Registry
clinicaltrials.gov
Start Date
February 23, 2021
End Date
July 2, 2024
Last Updated
10 months ago
Study Type
Interventional
Study Design
Single Group
Sex
Female

Investigators

Responsible Party
Principal Investigator
Principal Investigator

Department of Radiation Oncology

Principal Investigator

University of Maryland, Baltimore

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 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:

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

Arms & Interventions

Concurrent chemoradiation

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

Intervention: pelvic IMPT (Intensity Modulated Proton Therapy)

Concurrent chemoradiation

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

Intervention: carboplatin and paclitaxel

Outcomes

Primary Outcomes

Compliance rates

Time Frame: End of study, approximately 4 years

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

Secondary Outcomes

  • Acute GI and urinary toxicity(once a week during radiation treatment (5-6 weeks))
  • Late GI and urinary toxicity(6-month following radiation therapy)
  • Acute hematologic toxicity(Prior to each cycle of chemotherapy (once every 21 days for 106 days))

Study Sites (4)

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