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| ID | Type | Description | Link |
|---|---|---|---|
| UVA-LACC-PD201 | Other Grant/Funding Number | Merck Sharp & Dohme Corp. |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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The purpose of this study is to evaluate the safety and effectiveness of immunotherapy in combination with chemotherapy and radiation (chemoradiation) for the treatment of advanced cervical cancer. Pembrolizumab, a type of immunotherapy called a checkpoint inhibitor, will be administered after or during chemoradiation.
Primary: (1) To estimate the immunologic effects, as assessed in the tumor & PBMC, of both sequential and concurrent administration of pembrolizumab to CRT. Change between pre and post measurements of HPV E2, E7 specific CD8+ T cells, regulatory FoxP3+ T cells (Tregs) and the ratio of CD8+ T cells to Tregs are the immune measurements of primary interest. (2) To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer. Secondary: (1) To estimate rates of complete metabolic response on PET/CT imaging obtained 12 weeks after CRT.
(2) To estimate rates of distant metastasis as the first site of recurrence for patients.
(3) To estimate the influence of concurrent and consolidative MK-3475 on levels of plasminogen activator inhibitor-1 (PAI-1), a marker of immunosuppressive TGF-B.
(4) To estimate the influence of concurrent and consolidative MK-3475 on levels of IDO, an enzyme that depletes tryptophan, which is essential for T-cell function.
(5) To estimate the influence of concurrent and consolidative MK-3475 on levels of MHC class I (CD8+ T cell ligand) and MICA (NK ligand), as measured by MHC.
(6) To estimate the progression free survival (PFS) in subjects with locally advanced cervical cancer treated with sequential and concurrent administration of pembrolizumab in relation to CRT.
(7) To estimate the overall survival (OS) in subjects with locally advanced cervical cancer treated with sequential and concurrent administration of pembrolizumab in relation to CRT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Following chemoradiation | Experimental | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. After chemoradiation is complete, subjects will receive the study drug, pembrolizumab. |
|
| Concurrent to chemoradiation | Experimental | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Drug | 200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Immunologic Markers Following Combination of Study Drug With Chemoradiation | Expression of immune markers measured at pre and post administration of study drug with chemoradiation will be compared, analyzed and enumerated using QuPath software to provide a cell #/mm2 (not per high power field) and the ratio of CD8+ cells:FoxP3+ cells/mm2 was calculated. | 12 weeks post-chemoradiation |
| Number of Participants With Dose Limiting Toxicities | To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer | From start of treatment until 12 weeks post-chemoradiation |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolic Response Rate on PET/CT Imaging | To estimate rates of complete metabolic response on PET/CT imaging obtained 12 weeks after CRT | 12 weeks after chemotherapy |
| Incidence of Distant Metastases |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Linda Duska, MD | University of Virginia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of South Alabama Mitchell Cancer Institute | Mobile | Alabama | 36604 | United States | ||
| Johns Hopkins |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33581976 | Derived | Lin AJ, Dehdashti F, Massad LS, Thaker PH, Powell MA, Mutch DG, Schwarz JK, Markovina S, Siegel BA, Grigsby PW. Long-Term Outcomes of Cervical Cancer Patients Treated With Definitive Chemoradiation Following a Complete Metabolic Response. Clin Oncol (R Coll Radiol). 2021 May;33(5):300-306. doi: 10.1016/j.clon.2021.01.010. Epub 2021 Feb 11. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Following Chemoradiation | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. After chemoradiation is complete, subjects will receive the study drug, pembrolizumab. Pembrolizumab: 200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. Brachytherapy: Radiation is done for standard clinical care purposes. Cisplatin: 40 mg of chemotherapy drug will be given weekly for 5-6 weeks. |
| FG001 | Concurrent to Chemoradiation | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab. Pembrolizumab: 200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. Brachytherapy: Radiation is done for standard clinical care purposes. Cisplatin: 40 mg of chemotherapy drug will be given weekly for 5-6 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Following Chemoradiation | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. After chemoradiation is complete, subjects will receive the study drug, pembrolizumab. Pembrolizumab: 200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. Brachytherapy: Radiation is done for standard clinical care purposes. Cisplatin: 40 mg of chemotherapy drug will be given weekly for 5-6 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Immunologic Markers Following Combination of Study Drug With Chemoradiation | Expression of immune markers measured at pre and post administration of study drug with chemoradiation will be compared, analyzed and enumerated using QuPath software to provide a cell #/mm2 (not per high power field) and the ratio of CD8+ cells:FoxP3+ cells/mm2 was calculated. | Posted | Mean | Standard Deviation | ratio of cells per mm^2", "CD8+: FoxP3+ | 12 weeks post-chemoradiation |
|
Start of treatment (week 1) through end of treatment visit (35 +/- 5 days following the final treatment).
Adverse experiences will be graded according to NCI CTCAE Version 4.0. Toxicities will be characterized in terms regarding seriousness, causality, toxicity grading and action taken with regard to trial treatment. All adverse events will be reported according per protocol. Throughout the study, investigators should report any deaths, serious adverse events or other adverse events of concern they believe to be related to the investigational agent.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Following Chemoradiation | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. After chemoradiation is complete, subjects will receive the study drug, pembrolizumab. Pembrolizumab: 200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. Brachytherapy: Radiation is done for standard clinical care purposes. Cisplatin: 40 mg of chemotherapy drug will be given weekly for 5-6 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Linda R. Duska | University of Virginia | 434-944-9135 | LRD5D@uvahealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 6, 2018 | Apr 30, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 24, 2020 | Apr 30, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D001918 | Brachytherapy |
| D059248 | Chemoradiotherapy |
| D002945 | Cisplatin |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D003131 | Combined Modality Therapy |
| D017606 | Chlorine Compounds |
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|
| Brachytherapy | Radiation | Radiation is done for standard clinical care purposes. |
|
|
| Cisplatin | Drug | 40 mg of chemotherapy drug will be given weekly for 5-6 weeks. |
|
|
To estimate the rates of distant metastasis as the first site of recurrent for patients
| From start of treatment until up to 5 years following end of treatment |
| Progression Free Survival | To estimate the progression free survival (PFS) in subjects with locally advanced cervical cancer treatment with sequential and concurrent administration of pembrolizumab in relation to CRT | From start of treatment until up to 5 years following end of treatment |
| Overall Survival | To estimate the overall survival (OS) in subjects with locally advanced cervical cancer treated with sequential and concurrent administration of pembrolizumab in relation to CRT | From start of treatment until up to 5 years following end of treatment |
| Baltimore |
| Maryland |
| 21287 |
| United States |
| Washington University, School of Medicine | St Louis | Missouri | 63108 | United States |
| Levine Cancer Institute | Charlotte | North Carolina | 28204 | United States |
| University of Oklahoma | Oklahoma City | Oklahoma | 73104 | United States |
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
| INOVA Fairfax Hospital | Falls Church | Virginia | 22042 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| Non-Compliance |
|
| Disease Progression |
|
| Lost to Follow-up |
|
| BG001 | Concurrent to Chemoradiation | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab. Pembrolizumab: 200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. Brachytherapy: Radiation is done for standard clinical care purposes. Cisplatin: 40 mg of chemotherapy drug will be given weekly for 5-6 weeks. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Concurrent to Chemoradiation | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab. Pembrolizumab: 200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. Brachytherapy: Radiation is done for standard clinical care purposes. Cisplatin: 40 mg of chemotherapy drug will be given weekly for 5-6 weeks. |
|
|
| Primary | Number of Participants With Dose Limiting Toxicities | To determine the safety of concurrent chemoradiation in combination with pembrolizumab for the treatment of locally advanced cervical cancer | Subjects on Treatment | Posted | Count of Participants | Participants | From start of treatment until 12 weeks post-chemoradiation |
|
|
|
| Secondary | Metabolic Response Rate on PET/CT Imaging | To estimate rates of complete metabolic response on PET/CT imaging obtained 12 weeks after CRT | Subjects that completed Radiation Therapy within 56 days. | Posted | Count of Participants | Participants | 12 weeks after chemotherapy |
|
|
|
| Secondary | Incidence of Distant Metastases | To estimate the rates of distant metastasis as the first site of recurrent for patients | Number of subjects on treatment | Posted | Count of Participants | Participants | From start of treatment until up to 5 years following end of treatment |
|
|
|
| Secondary | Progression Free Survival | To estimate the progression free survival (PFS) in subjects with locally advanced cervical cancer treatment with sequential and concurrent administration of pembrolizumab in relation to CRT | Number of Subjects on Treatment | Posted | Count of Participants | Participants | From start of treatment until up to 5 years following end of treatment |
|
|
|
| Secondary | Overall Survival | To estimate the overall survival (OS) in subjects with locally advanced cervical cancer treated with sequential and concurrent administration of pembrolizumab in relation to CRT | Number of subjects on treatment | Posted | Count of Participants | Participants | From start of treatment until up to 5 years following end of treatment |
|
|
|
| 8 |
| 48 |
| 40 |
| 48 |
| 18 |
| 48 |
| EG001 | Concurrent to Chemoradiation | Subjects will receive standard chemotherapy weekly and 4-6 fractions of brachytherapy radiation for 5-6 weeks. While subjects are receiving chemotherapy and radiation, they will also receive the study drug, pembrolizumab. Pembrolizumab: 200 mg of study drug is given through intravenous (IV) administration once every 21 days for 3 months. Brachytherapy: Radiation is done for standard clinical care purposes. Cisplatin: 40 mg of chemotherapy drug will be given weekly for 5-6 weeks. | 5 | 46 | 27 | 46 | 11 | 46 |
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
|
| Colonic obstruction | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrointestinal Pain | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomitng | Gastrointestinal disorders | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
|
| Allergic Reaction | Immune system disorders | Systematic Assessment |
|
| Kidney Infection | Infections and infestations | Systematic Assessment |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
|
| Chronic kidney disease | Renal and urinary disorders | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | Systematic Assessment |
|
| Thromboembolic event | Vascular disorders | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
|
| Colonic stenosis | Gastrointestinal disorders | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Flu like symptoms | General disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Blurred Vision | Eye disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Urinary Tract Infection | Renal and urinary disorders | Systematic Assessment |
|
| Creatinine increased | Investigations | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
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| D009369 |
| Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D007287 |
| Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |