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External Beam Radiation Therapy and Brachytherapy With Chemotherapy and Immunotherapy for the Treatment of Stage IVB Cervical Cancer

RecruitingPhase 1, Phase 2Ages 18 Years - anyAllJonsson Comprehensive Cancer Center
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In plain words

What the trial is, and whether it could suit you

This phase I/II trial tests the safety and effectiveness of receiving external beam radiation therapy (EBRT) and brachytherapy along with chemotherapy, consisting of cisplatin and paclitaxel, and immunotherapy, consisting of bevacizumab and pembrolizumab, for the treatment of patients with stage IVB cervical cancer. EBRT is type of radiation therapy that uses a machine to aim high-energy rays at the cancer from outside of the body. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It 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. Bevacizumab is in a class of medication

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📋 Eligibility rules (as published)
Inclusion Criteria: * Participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of Stage IVB cervical cancer will be enrolled in this study * Patients with stage IVB adenocarcinoma, adenosquamous carcinoma, or squamous-cell carcinoma of the cervix that has not yet been treated with systemic chemotherapy or radiation therapy * Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤ grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤ grade 2 neuropathy are eligible * The participant provides written informed consent for the trial * Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions * Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue * Patients must have PD-L1 status, CPS score of over 1. PD-L1 status will be determined per institutional standards via the Food and Drug Administration (FDA)-approved test, Dako PD-L1 immunohistochemistry (IHC) 22C3 pharmDx kit with combined positive score (CPS) interpretation * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) anti-viral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization. Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests are not required unless: * Known history of HBV infection * As mandated by local health authority * Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening. Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization. Hepatitis C screening tests are not required unless: * Known history of HCV infection * As mandated by local health authority * HIV-infected participants must have well-controlled HIV on antiretroviral treatment (ART), defined as: * Participants on ART must have a CD4+ T-cell count ≥ 350 cells/mm\^3 at the time of screening * Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening * It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months. * Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (day 1) and agree to continue ART throughout the study * The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers) * Absolute neutrophil count (ANC) ≥ 1500/µL (collected within 10 days prior to the start of study) * Platelets ≥ 100 000/µL (collected within 10 days prior to the start of study) * Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (collected within 10 days prior to the start of study). Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks * Creatinine ≤ 1.5 × upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) ≥ 30 mL/min for participant with creatinine levels \> 1.5 × institutional ULN (collected within 10 days prior to the start of study) * Creatinine clearance (CrCl) should be calculated per institutional standard * Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 × ULN (collected within 10 days prior to the start of study) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases) (collected within 10 days prior to the start of study) * International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants (collected within 10 days prior to the start of study) Exclusion Criteria: * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) * Has received prior hysterectomy. (Prior lymphadenectomy permitted) * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks to /allocation * Has received prior radiotherapy for cervical cancer * Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed * Has received an investigational agent or has used an
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What it tests

  • Bevacizumab
  • Biospecimen Collection
  • Brachytherapy
  • Cisplatin
  • External Beam Radiation Therapy
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Where

4 sites
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, United States
University of California San Diego (UCSD)
San Diego, United States
University of Oklahoma Health Sciences Center
Oklahoma City, United States
University of Virginia Cancer Center
Charlottesville, United States
🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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