Cisplatin-based Hypofractionated Radiation Therapy followed by Brachytherapy in Treating Patients with Bulky or Metastatic Cervical Cancer

Inclusion Criteria

• Pathologically or cytologically-confirmed diagnosis of Federation of Gynecology and Obstetrics (FIGO) stage IB3, II, or IIIA-IIIC1 bulky (≥ 6cm) or stage IVA or stage IVB (FIGO 2018) squamous, adenosquamous, or adenocarcinoma of the uterine cervix with limited metastatic burden (not requiring urgent systemic therapy). * Note: Stage IVA and/or IVB patients are not required to have bulky ( ≥ 6cm) disease. * NOTE: Prior chemotherapy for this tumor/disease is allowed.
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelets >= 75,000/uL
• Hemoglobin >= 9 g/dL * Patients whose hemoglobin is < 9 g/dL may receive transfusions per institutional guidelines to meet eligibility criteria
• Creatinine =< 1.5 mg/dL to receive weekly cisplatin or creatinine clearance (CrCl) >= 30 ml/minute * Patients with creatinine between 1.5 - 1.9 mg/dL are eligible for cisplatin administration if the following 2 conditions are met: ** No hydronephrosis and ** Creatinine clearance is >= 30 ml/minute estimated by Cockcroft-Gault formula
• Age ≥ 18 years
• Gynecologic Oncology Group performance status of 0, 1, or 2
• Patient agrees to use two forms of birth control if they are of child-bearing potential. Cisplatin and radiation are known teratogens. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, throughout duration of active treatment and for two months after completion of chemotherapy or radiation (i.e., last dose of either). * Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Concomitant administration of pembrolizumab is allowed per discretion of the treating physician. Patients already on pembrolizumab may continue to receive pembrolizumab

Exclusion Criteria

• Presence of another concurrent active invasive malignancy
• Prior invasive malignancy diagnosed within the last three years, with the following two exceptions: * Non-melanoma skin cancer and/or * Prior in situ carcinoma of the cervix
• Receipt of prior pelvic radiotherapy for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, at the discretion of the treating physician
• Currently receiving any other investigational agent(s) for the treatment of cancer
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin or other agents used in study
• Excluded if presence of uncontrolled intercurrent illness as determined by the treating physician which includes, but is not limited to: * Exclusions related to uncontrolled intercurrent illness: ** Renal *** Clinically significant renal function impairment (creatinine >= 2 mg/dL) ** Cardiac *** Symptomatic congestive heart failure *** Unstable angina pectoris *** Myocardial infarction within six months of treatment initiation *** Cardiac arrhythmia within six months of treatment initiation *** Known inadequately controlled hypertension ** Pulmonary *** Clinically significant pulmonary disease including dyspnea at rest *** Patients requiring supplemental oxygen *** Poor pulmonary reserve leading to inability to tolerate anesthesia for brachytherapy ** Psychiatric *** Psychiatric illness/social situations that would limit compliance with study requirements
• Excluded if pregnant or lactating
• Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better