Endometrial Cancer
Conditions
Keywords
Endometrial cancer, Gynecologic cancers, Radiotherapy, Proton Therapy, Chemotherapy, Chemoradiation
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.
Interventions
carboplatin and paclitaxel 5-6 cycles (dosage per standard of care according to treating oncologist)
RADIATIONpelvic IMPT (Intensity Modulated Proton Therapy)
whole pelvis will receive a total dose of 4500 cGy in 25 fractions to 5040 cGy in 28 fractions
Sponsors
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Completed Full 6 Cycles of Chemotherapy Concurrently With IMPT | End of study, approximately 4 years | This will be measured as proportion of patients completing full 6 cycles of chemotherapy concurrently with IMPT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Acute GI and Urinary Toxicity | once a week during radiation treatment, up to 5-6 weeks | Measured by CTCAE (Common Terminology Criteria for Adverse Events). Toxicities noted did not meet the criteria for Serious Adverse Event. No SAEs noted. |
| Number of Participants With Acute GI and Urinary Toxicity Measured by PRO-CTCAE | once a week during radiation treatment, up to 5-6 weeks | Measured by PRO-CTCAE (Patient reported outcomes Common Terminology Criteria for Adverse Events) |
| Number of Participants With Acute GI and Urinary Toxicity Measured by EPIC | once a week during radiation treatment, up to 5-6 weeks | Measured by EPIC (Expanded Prostate Cancer Index Composite ) bowel and urinary domain |
| Number of Participants With Acute Hematologic Toxicity | Prior to each cycle of chemotherapy (once every 21 days for 106 days) | Measured by CTCAE (Common Terminology Criteria for Adverse Events). Toxicities noted did not meet the criteria for Serious Adverse Event. No SAEs noted. |
| Number of Participants With Late GI and Urinary Toxicity | 6-month following radiation therapy | Measured by CTCAE (Common Terminology Criteria for Adverse Events) |
| Number of Participants With Late GI and Urinary Toxicity Per PRO-CTCAE | 6-month following radiation therapy | Measured by PRO-CTCAE (Patient reported outcomes Common Terminology Criteria for Adverse Events) |
| Number of Participants With Late GI and Urinary Toxicity Measured by EPIC | 6-month following radiation therapy | Measured by EPIC (Expanded Prostate Cancer Index Composite ) bowel and urinary domain |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPranshu Mohindra, MD
University of Maryland/Maryland Proton Treatment Center
Participant flow
Recruitment details
Recruitment ended early due to low accrual, study terminated before outcome measure data was collected.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 58 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 2 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
None listed