Clinical trial NCT04527900: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: Endometrial cancer
Gynecologic cancers
Radiotherapy
Proton Therapy
Chemotherapy
Chemoradiation
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2020-08-27
Enrollment: 21
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Compliance rates
timeFrame: End of study, approximately 4 years
Secondary outcomes:
measure: Acute GI and urinary toxicity
timeFrame: once a week during radiation treatment (5-6 weeks)
measure: Acute GI and urinary toxicity
timeFrame: once a week during radiation treatment (5-6 weeks)
measure: Acute GI and urinary toxicity
timeFrame: once a week during radiation treatment (5-6 weeks)
measure: Acute hematologic toxicity
timeFrame: Prior to each cycle of chemotherapy (once every 21 days for 106 days)
measure: Late GI and urinary toxicity
timeFrame: 6-month following radiation therapy
measure: Late GI and urinary toxicity
timeFrame: 6-month following radiation therapy
measure: Late GI and urinary toxicity
timeFrame: 6-month following radiation therapy
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Maryland Proton Treatment Center
state: Maryland
city: Baltimore
country: United States
facility: UMMC
state: Maryland
city: Columbia
country: United States
facility: Central Maryland Radiation Oncology
state: Maryland
city: Glen Burnie
country: United States
facility: Baltimore Washington Medical Center
state: Maryland
Study officials:
affiliation: University of Maryland/Maryland Proton Treatment Center
name: Pranshu Mohindra, MD
role: PRINCIPAL_INVESTIGATOR
References: