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Carboplatin and Paclitaxel in Combination with Short-Course Radiation Therapy for the Treatment of Women with Newly Diagnosed Stage III Endometrial Cancer
Trial Status: active
This early phase I trial tests the safety, side effects, and how well carboplatin and paclitaxel in combination with short-course radiation therapy work in treating women with newly diagnosed stage III endometrial cancer. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. The radiation therapy being used in the study is called intensity-modulated external beam radiation therapy (IMRT). It is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of a tumor. IMRT delivers radiation directly to tumor cells from different angles by changing the radiation beam into multiple smaller beams. By targeting the tumor, IMRT reduces radiation damage to healthy tissue. The researchers think that a shorter schedule of 1 week of radiation therapy will allow the patient to get the most benefit from both chemotherapy (decreasing the chance of cancer coming back anywhere in the body) and radiation therapy (decreasing the chance of cancer coming back in the pelvis).
Inclusion Criteria
Patients must have newly diagnosed endometrial carcinoma. The following histologic subtypes are eligible for inclusion: endometrioid, serous, clear cell, dedifferentiated/undifferentiated, mixed epithelial, adenocarcinoma not otherwise specified, and carcinosarcoma
Surgery must have included a hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node surgical assessment (sentinel lymph node mapping and/or sampling). Para-aortic lymph node surgical assessment is optional
Patients must have Federation of Gynecology and Obstetrics (FIGO) (2009) stage IIIA or IIIC1 disease (as determined by surgical staging)
Patients must consent to testing with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) part A and are encouraged to consent to both parts A and C
Age >= 18 years
Patients must have an Karnofsky Performance Status (KPS) >= 70 (or Eastern Cooperative Oncology Group ECOG 0 or 1)
Neurologic function: Neuropathy (sensory and motor) grade =< 1
No residual gross disease after surgery
No prior radiation therapy or chemotherapy for treatment of endometrial cancer
No active infection requiring antibiotics, except for uncomplicated urinary tract infection
Absolute neutrophil count (ANC) >= 1500/mcL (no more than 14 days prior to first study treatment)
Platelet count >= 100,000/mcL (no more than 14 days prior to first study treatment)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3X upper limit of normal (ULN) (no more than 14 days prior to first study treatment)
Total bilirubin =< 1.5X ULN. Patients with known Gilbert’s disease and a total bilirubin =< 3X ULN may be enrolled (no more than 14 days prior to first study treatment)
Creatinine =< 1.5X ULN (no more than 14 days prior to first study treatment)
Entry into study is limited to no more than 12 weeks from the date of surgery
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients of childbearing age will by definition have undergone hysterectomy and bilateral oophorectomy prior to study enrollment
Participants must agree not to breastfeed during the study or for 150 days after the last dose of study treatment
Exclusion Criteria
Patients whose endometrial cancers harbor known pathogenic POLE mutations
Patients whose endometrial cancers are mismatch repair deficient, as determined by immunohistochemical staining for MLH1, PMS2, MSH2, and MSH6 and/or microsatellite instability high (MSI-H)
Active inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. This includes but is not limited to: uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, and superior vena cava syndrome
Patients unfit for pelvic radiation therapy due to the following:
* Has had radiation therapy encompassing >20% of the bone marrow within 2 weeks, or any radiation therapy within 1 week prior to day 1 of protocol therapy
* Patients with a history of pelvic radiation
* Patients with a history or current diagnosis of a vesicovaginal, enterovaginal, or colovaginal fistula
* Any hematological abnormality or disorder that would be a contraindication to radiation per the treating physician
Additional locations may be listed on ClinicalTrials.gov for NCT05691010.
I. To evaluate the feasibility of integrated delivery of short-course IMRT with carboplatin/paclitaxel in patients with stage III endometrial cancer, defined as completion of all 6 planned cycles of carboplatin and paclitaxel with no delays in chemotherapy cycles greater than 21 days.
SECONDARY OBJECTIVES:
I. To determine the safety and tolerability of integrated delivery of short-course IMRT with carboplatin/paclitaxel in patients with stage III endometrial cancer, as measured by incidence of acute (occurring within 6 months of start of protocol therapy) and late (occurring 6 months or later after start of protocol therapy) toxicities.
II. To evaluate quality of life after integrated delivery of short-course IMRT with carboplatin/paclitaxel.
III. To evaluate progression free survival (PFS) at 24 months, defined as the duration of time from start of protocol therapy to time of recurrence, progression, or death due to any cause, whichever occurs first.
IV. To determine the rates of isolated locoregional failure, defined as recurrence within the vaginal cuff or pelvic lymph nodes, and distant metastatic failure.
V. To evaluate overall survival (OS) at 24 months, defined as the duration of time from the start of protocol therapy until death due to any cause.
OUTLINE:
Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After cycles 1, 2, 3 or 4, patients then undergo short-course IMRT five days a week, for 1 week at the discretion of the treating radiation oncologist. Patients also undergo chest imaging with X-ray throughout the trial, and abdominal/pelvic imaging with computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.
After completion of study treatment, patients are followed up at 30 days, and then at 6, 12, 18 and 24 months.
Trial PhasePhase O
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
