This study is currently recruiting participants.
Number
001778-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Fetuses;Male;Pregnant Women;Neonates
Keywords
Human Papilloma Virus; Cervical Cancer; Pembrolizumab; Therapeutic Vaccine; Cervix Cancer; Resistance to Checkpoint Inhibitors
Recruitment Keyword(s)
None
Condition(s)
Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Cervical Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
Investigational Drug(s)
MK-3475 (Pembrolizumab) PRGN-2009 (gorilla-derived adenovirus-expressing HPV-16/18 E6/E7 vaccine)
Investigational Device(s)
Intervention(s)
Biological/Vaccine: PRGN-2009 Drug: Pembrolizumab
Supporting Site
National Cancer Institute
Cervical cancer is the 4th leading cause of death in women worldwide. More than 90% of women survive more than 5 years when the disease is treated in its earliest stages. But if the disease returns or spreads, only about 17% of women survive 5 years. Better treatments are needed.
Objective:
To test a new drug (PRGN-2009) combined with pembrolizumab vs pembrolizumab alone in women with cervical cancer.
Eligibility:
Women aged 18 years or older with cervical cancer that came back or spread after treatment with pembrolizumab.
Design:
Participants will be screened. They will have blood tests, chest x-rays, imaging scans, and tests of heart function. They will have a biopsy: A tissue sample will be taken from their tumor.
Pembrolizumab is given through a tube attached to a needle inserted into a vein. All participants will receive this drug every 6 weeks.
PRGN-2009 is injected under the skin. Half of participants will get both drugs. The first 3 doses of PRGN-2009 will be given at 3-week intervals; after that, participants will get the injections every 6 weeks.
All participants will have regular clinic visits. Blood tests, biopsies, and imaging scans will be repeated. They may also give nasal swabs, skin swabs, urine, and stool samples.
If their disease progresses, participants who were not getting PRGN-2009 may begin taking that study drug.
Participants may remain in the study as long as the treatment is helping them. If they stop taking the study drugs, follow-up visits will continue every 12 weeks for up to 5 years. These visits may be in person or by phone.
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INCLUSION CRITERIA: -Age 18 years and older. -Recurrent or metastatic cervical cancer (histologically or cytologically confirmed) that meets the criteria of resistant to pembrolizumab -Must have been treated with pembrolizumab, either as monotherapy or in combination, for at least 6 weeks --Patients that discontinued pembrolizumab treatment due to an adverse event or have an ongoing adverse event (> Grade 2) due to pembrolizumab treatment are ineligible for the study. -Subjects must have received no more than three prior systemic regimens. -Subjects must have histologically or cytologically confirmed HPV positive disease confirmed by using at least one of the following methods: --Medical history of any positive HPV result using an FDA approved assay --Any level of p16 overexpression on a tumor biopsy will be accepted for eligibility --Positive HPV result using FDA approved assay if the disease is amenable to a cervical or vault smear -Tumors are confirmed positive for PD-L1 with a combined positive score of >= 1 by using one of the following methods: --A newly obtained tumor biopsy evaluated for PD-L1 using an FDA approved test. --If it is not possible to obtain a fresh biopsy, a pathology report from a biopsy of any tumor lesion that has been evaluated for PD-L1, can be used for eligibility. -Measurable disease that can be accurately measured by RECIST v1.1 criteria in at least one dimension as >=1.0 cm or 1.5 cm for lymph nodes. Note: Previously irradiated lesions cannot be considered target lesions. -Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. -Life expectancy >= 12 weeks from the time of enrollment. -Must have adequate organ function, as determined by the following values: --Hematological lab values determined within 14 days of treatment: ---Absolute neutrophil count (ANC) >= 1,500 /microL ---Platelets >=100,000 / microL ---Hemoglobin >= 9 g/dL (patients must not have had transfusion or erythropoietin [EPO] within 4 weeks) --Serum creatinine (Cr) < 2.0 x upper limit of normal (ULN) or calculated or measured creatinine clearance (absolute value) of >= 40 mL/minute or Cr. GFR can also be used in place of creatinine or CrCl. --Serum total bilirubin <= 2.0 x ULN or direct bilirubin <= 1.0 x ULN for patients with elevated total bilirubin. --Alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT) < 2.5 x ULN (or < 5 x ULN for patients with liver metastases). --Ejection fraction measured by echocardiogram (ECHO) or multigated acquisition scan (MUGA) > 45%. --International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) <= 1.5 x ULN, or if patient is receiving anticoagulant therapy, PT or aPTT is within therapeutic range of intended use of anticoagulants. --Thyroid stimulating hormone <= 1.0 x ULN. -Patient does not require supplemental oxygen or mechanical ventilation and has an oxygen saturation of >= 92% or higher on room air. -Negative serum pregnancy test. Persons of child-bearing potential (POCBP) must agree to use adequate contraception prior to study entry and for at least 6 months following completion of study treatment. -All patients must have the ability to understand and willingness to sign a written informed consent. EXCLUSION CRITERIA: Patients will be excluded from entry to the study if any of the following criteria are met: -Prior chemotherapy, targeted small molecule therapy, or radiation therapy with the intent to treat within 14 days of start of treatment; an antineoplastic monoclonal antibody within prior 4 weeks, or has not recovered from (i.e., <= Grade 1) adverse events caused by prior treatment. --Radiation therapy in a palliative setting or local radiation (ex. radiation therapy for one or more lesions for symptom control in subjects with multiple lesions provided that not all lesions are irradiated) is allowed prior to treatment. -Patients with a diagnosis of immunodeficiency, patients with active autoimmune disease requiring systemic immunosuppressive therapy (i.e., > 10 mg of prednisone daily or equivalent), or patients who have received any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Note: patients with HIV are eligible if they have sufficient disease control, in the opinion of the investigator. -Active hepatitis B (positive HBsAg test) or hepatitis C (positive HCV RTPCR) infection based on testing performed within 30 days of enrollment. -History of pneumonitis or interstitial lung disease. -Has received a live vaccine within 30 days prior to the first dose of study drug. -Patients with presence of other active malignancy within 1 year prior to study entry; patients with adequately resected basal or squamous cell carcinoma of the skin may enroll irrespective of the time of diagnosis. -Known central nervous system (CNS) disease. -Has severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients. -Known history of active tuberculosis (TB, Bacillus tuberculosis). -Pregnant and lactating women are excluded from this study. -Patients with a history of solid organ transplant. -Patients currently participating in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment. -Patients, who in the opinion of the investigator, may not be able to comply with the monitoring requirements of the study. -Patients with uncontrolled serious infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, poorly controlled pulmonary disease, psychiatric illness/social situations serious illness, or any other medical condition, which in the investigator s opinion would interfere with the patient s participation in the study, or with the interpretation of the results.
-Age 18 years and older.
-Recurrent or metastatic cervical cancer (histologically or cytologically confirmed) that meets the criteria of resistant to pembrolizumab
-Must have been treated with pembrolizumab, either as monotherapy or in combination, for at least 6 weeks
--Patients that discontinued pembrolizumab treatment due to an adverse event or have an ongoing adverse event (> Grade 2) due to pembrolizumab treatment are ineligible for the study.
-Subjects must have received no more than three prior systemic regimens.
-Subjects must have histologically or cytologically confirmed HPV positive disease confirmed by using at least one of the following methods:
--Medical history of any positive HPV result using an FDA approved assay
--Any level of p16 overexpression on a tumor biopsy will be accepted for eligibility
--Positive HPV result using FDA approved assay if the disease is amenable to a cervical or vault smear
-Tumors are confirmed positive for PD-L1 with a combined positive score of >= 1 by using one of the following methods:
--A newly obtained tumor biopsy evaluated for PD-L1 using an FDA approved test.
--If it is not possible to obtain a fresh biopsy, a pathology report from a biopsy of any tumor lesion that has been evaluated for PD-L1, can be used for eligibility.
-Measurable disease that can be accurately measured by RECIST v1.1 criteria in at least one dimension as >=1.0 cm or 1.5 cm for lymph nodes. Note: Previously irradiated lesions cannot be considered target lesions.
-Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
-Life expectancy >= 12 weeks from the time of enrollment.
-Must have adequate organ function, as determined by the following values:
--Hematological lab values determined within 14 days of treatment:
---Absolute neutrophil count (ANC) >= 1,500 /microL
---Platelets >=100,000 / microL
---Hemoglobin >= 9 g/dL (patients must not have had transfusion or erythropoietin [EPO] within 4 weeks)
--Serum creatinine (Cr) < 2.0 x upper limit of normal (ULN) or calculated or measured creatinine clearance (absolute value) of >= 40 mL/minute or Cr. GFR can also be used in place of creatinine or CrCl.
--Serum total bilirubin <= 2.0 x ULN or direct bilirubin <= 1.0 x ULN for patients with elevated total bilirubin.
--Alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT) < 2.5 x ULN (or < 5 x ULN for patients with liver metastases).
--Ejection fraction measured by echocardiogram (ECHO) or multigated acquisition scan (MUGA) > 45%.
--International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) <= 1.5 x ULN, or if patient is receiving anticoagulant therapy, PT or aPTT is within therapeutic range of intended use of anticoagulants.
--Thyroid stimulating hormone <= 1.0 x ULN.
-Patient does not require supplemental oxygen or mechanical ventilation and has an oxygen saturation of >= 92% or higher on room air.
-Negative serum pregnancy test. Persons of child-bearing potential (POCBP) must agree to use adequate contraception prior to study entry and for at least 6 months following completion of study treatment.
-All patients must have the ability to understand and willingness to sign a written informed consent.
EXCLUSION CRITERIA:
Patients will be excluded from entry to the study if any of the following criteria are met:
-Prior chemotherapy, targeted small molecule therapy, or radiation therapy with the intent to treat within 14 days of start of treatment; an antineoplastic monoclonal antibody within prior 4 weeks, or has not recovered from (i.e., <= Grade 1) adverse events caused by prior treatment.
--Radiation therapy in a palliative setting or local radiation (ex. radiation therapy for one or more lesions for symptom control in subjects with multiple lesions provided that not all lesions are irradiated) is allowed prior to treatment.
-Patients with a diagnosis of immunodeficiency, patients with active autoimmune disease requiring systemic immunosuppressive therapy (i.e., > 10 mg of prednisone daily or equivalent), or patients who have received any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Note: patients with HIV are eligible if they have sufficient disease control, in the opinion of the investigator.
-Active hepatitis B (positive HBsAg test) or hepatitis C (positive HCV RTPCR) infection based on testing performed within 30 days of enrollment.
-History of pneumonitis or interstitial lung disease.
-Has received a live vaccine within 30 days prior to the first dose of study drug.
-Patients with presence of other active malignancy within 1 year prior to study entry; patients with adequately resected basal or squamous cell carcinoma of the skin may enroll irrespective of the time of diagnosis.
-Known central nervous system (CNS) disease.
-Has severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients.
-Known history of active tuberculosis (TB, Bacillus tuberculosis).
-Pregnant and lactating women are excluded from this study.
-Patients with a history of solid organ transplant.
-Patients currently participating in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment.
-Patients, who in the opinion of the investigator, may not be able to comply with the monitoring requirements of the study.
-Patients with uncontrolled serious infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, poorly controlled pulmonary disease, psychiatric illness/social situations serious illness, or any other medical condition, which in the investigator s opinion would interfere with the patient s participation in the study, or with the interpretation of the results.
Principal Investigator
Referral Contact
For more information: