Trial Title:
External Beam Radiation Therapy and Brachytherapy With Chemotherapy and Immunotherapy for the Treatment of Stage IVB Cervical Cancer
NCT ID:
NCT06543576
Condition:
Cervical Adenocarcinoma
Cervical Adenosquamous Carcinoma
Cervical Squamous Cell Carcinoma
Stage IVB Cervical Cancer American Joint Committee on Cancer (AJCC) v8
Conditions: Official terms:
Carcinoma
Uterine Cervical Neoplasms
Carcinoma, Adenosquamous
Paclitaxel
Bevacizumab
Cisplatin
Pembrolizumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Immunological
Endothelial Growth Factors
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunoglobulin G
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Bevacizumab
Description:
Given IV
Arm group label:
Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy)
Other name:
ABP 215
Other name:
ABP-215
Other name:
ABP215
Other name:
Alymsys
Other name:
Anti-VEGF
Other name:
Anti-VEGF Humanized Monoclonal Antibody
Other name:
Anti-VEGF Monoclonal Antibody SIBP04
Other name:
Anti-VEGF rhuMAb
Other name:
Avastin
Other name:
Aybintio
Other name:
BAT 1706
Other name:
BAT-1706
Other name:
BAT1706
Other name:
BAT1706 Biosimilar
Other name:
Bevacizumab awwb
Other name:
Bevacizumab Biosimilar ABP 215
Other name:
Bevacizumab Biosimilar BAT1706
Other name:
Bevacizumab Biosimilar BEVZ92
Other name:
Bevacizumab Biosimilar BI 695502
Other name:
Bevacizumab Biosimilar CBT 124
Other name:
Bevacizumab Biosimilar CT-P16
Other name:
Bevacizumab Biosimilar FKB238
Other name:
Bevacizumab Biosimilar GB-222
Other name:
Bevacizumab Biosimilar HD204
Other name:
Bevacizumab Biosimilar HLX04
Other name:
Bevacizumab Biosimilar IBI305
Other name:
Bevacizumab Biosimilar LY01008
Other name:
Bevacizumab Biosimilar MIL60
Other name:
Bevacizumab Biosimilar Mvasi
Other name:
Bevacizumab Biosimilar MYL-1402O
Other name:
Bevacizumab Biosimilar QL 1101
Other name:
Bevacizumab Biosimilar QL1101
Other name:
Bevacizumab Biosimilar RPH-001
Other name:
Bevacizumab Biosimilar SCT501
Other name:
Bevacizumab Biosimilar Zirabev
Other name:
Bevacizumab-adcd
Other name:
Bevacizumab-awwb
Other name:
Bevacizumab-aybi
Other name:
Bevacizumab-bvzr
Other name:
Bevacizumab-equi
Other name:
Bevacizumab-maly
Other name:
Bevacizumab-onbe
Other name:
BP102
Other name:
BP102 Biosimilar
Other name:
CT P16
Other name:
CT-P16
Other name:
CTP16
Other name:
Equidacent
Other name:
HD204
Other name:
Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
Other name:
Mvasi
Other name:
MYL-1402O
Other name:
Onbevzi
Other name:
QL1101
Other name:
Recombinant Humanized Anti-VEGF Monoclonal Antibody
Other name:
rhuMab-VEGF
Other name:
SCT501
Other name:
SIBP 04
Other name:
SIBP-04
Other name:
SIBP04
Other name:
Vegzelma
Other name:
Zirabev
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Radiation
Intervention name:
Brachytherapy
Description:
Undergo brachytherapy
Arm group label:
Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy)
Other name:
Brachytherapy, NOS
Other name:
Internal Radiation
Other name:
Internal Radiation Brachytherapy
Other name:
Internal Radiation Therapy
Other name:
Radiation Brachytherapy
Other name:
Radiation, Internal
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Given IV
Arm group label:
Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy)
Other name:
Abiplatin
Other name:
Blastolem
Other name:
Briplatin
Other name:
CDDP
Other name:
Cis-diammine-dichloroplatinum
Other name:
Cis-diamminedichloridoplatinum
Other name:
Cis-diamminedichloro Platinum (II)
Other name:
Cis-diamminedichloroplatinum
Other name:
Cis-dichloroammine Platinum (II)
Other name:
Cis-platinous Diamine Dichloride
Other name:
Cis-platinum
Other name:
Cis-platinum II
Other name:
Cis-platinum II Diamine Dichloride
Other name:
Cismaplat
Other name:
Cisplatina
Other name:
Cisplatinum
Other name:
Cisplatyl
Other name:
Citoplatino
Other name:
Citosin
Other name:
Cysplatyna
Other name:
DDP
Other name:
Lederplatin
Other name:
Metaplatin
Other name:
Neoplatin
Other name:
Peyrone's Chloride
Other name:
Peyrone's Salt
Other name:
Placis
Other name:
Plastistil
Other name:
Platamine
Other name:
Platiblastin
Other name:
Platiblastin-S
Other name:
Platinex
Other name:
Platinol
Other name:
Platinol- AQ
Other name:
Platinol-AQ
Other name:
Platinol-AQ VHA Plus
Other name:
Platinoxan
Other name:
Platinum
Other name:
Platinum Diamminodichloride
Other name:
Platiran
Other name:
Platistin
Other name:
Platosin
Intervention type:
Radiation
Intervention name:
External Beam Radiation Therapy
Description:
Undergo EBRT
Arm group label:
Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy)
Other name:
Definitive Radiation Therapy
Other name:
EBRT
Other name:
External Beam Radiation
Other name:
External Beam Radiotherapy
Other name:
External Beam Radiotherapy (conventional)
Other name:
External Beam RT
Other name:
external radiation
Other name:
External Radiation Therapy
Other name:
external-beam radiation
Other name:
Radiation, External Beam
Other name:
Teleradiotherapy
Other name:
Teletherapy
Other name:
Teletherapy Radiation
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Given IV
Arm group label:
Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy)
Other name:
Anzatax
Other name:
Asotax
Other name:
Bristaxol
Other name:
Praxel
Other name:
Taxol
Other name:
Taxol Konzentrat
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy)
Other name:
BCD-201
Other name:
GME 751
Other name:
GME751
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK 3475
Other name:
MK-3475
Other name:
MK3475
Other name:
Pembrolizumab Biosimilar BCD-201
Other name:
Pembrolizumab Biosimilar GME751
Other name:
Pembrolizumab Biosimilar QL2107
Other name:
QL2107
Other name:
SCH 900475
Other name:
SCH-900475
Other name:
SCH900475
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary study
Arm group label:
Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy)
Summary:
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 medications called antiangiogenic agents. It works by
stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This
may slow the growth and spread of tumor. A monoclonal antibody, such as pembrolizumab, is
a type of protein that can bind to certain targets in the body, such as molecules that
cause the body to make an immune response (antigens). Giving EBRT and brachytherapy along
with chemotherapy and immunotherapy may be a safe and effective way to treat patients
with stage IVB cervical cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To demonstrate that radiotherapy can be safely integrated into chemotherapy and
pembrolizumab with bevacizumab in newly diagnosed stage IVB cervical cancer to improve
outcomes.
SECONDARY OBJECTIVE:
I. To demonstrate improvements with overall response rate, overall survival (OS), and
duration of response with the addition of radiation therapy to standard of care in stage
IVB cervical cancer.
EXPLORATORY OBJECTIVES:
I. To demonstrate improved quality of life and disease-related toxicity with the addition
of radiation therapy to standard of care chemotherapy in stage IVB cervical cancer.
II. To explore the association of known risk factors (age, race/ethnicity, smoking
status, baseline quality of life, combined positive score [CPS] score 1-10 versus > 10,
and performance status with the change in QOL, treatment outcomes, and toxicities.
III. To explore circulating tumor deoxyribonucleic acid (ctDNA) as a biomarker to monitor
the response to upfront chemotherapy-immunotherapy and subsequent radiation.
IV. To use T cell receptor repertoire sequencing (TCRseq) to define T cell clones present
in the tumor and to establish their concordance with peripheral blood T cell clones at
baseline and in response to therapy.
OUTLINE:
PART 1: Patients receive cisplatin intravenously (IV), paclitaxel IV, pembrolizumab IV
over 30 minutes, and bevacizumab IV on day 1 of each cycle. Cycles repeat every 21 days
for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients
receive no treatment for 3 weeks.
PART 2: Patients undergo EBRT for 25 treatments delivered over 5 weeks, and brachytherapy
over 3-5 treatments. Patients also receive pembrolizumab IV over 30 minutes and
bevacizumab IV on day 1 of each cycle. Cycles for immunotherapy repeat every 21 days for
a total of 2 years in the absence of disease progression or unacceptable toxicity.
Participants who complete study intervention after 2 years of pembrolizumab are eligible
for up to 1 year of additional pembrolizumab (second course) upon experiencing disease
progression.
Patients undergo computed tomography (CT), positron emission tomography (PET)/CT, and/or
magnetic resonance imaging (MRI) throughout the study. Patients also undergo blood sample
collection throughout the study.
After completion of study treatment, patients follow up at 30 days and every 6 weeks for
up to 1 year then every 9 weeks.
Criteria for eligibility:
Criteria:
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-inte
ractions-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 investigational device within 4
weeks prior to study intervention administration
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug
- Known additional malignancy that is progressing or has required active treatment
within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in
situ of the bladder, that have undergone potentially curative therapy are not
excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason
score ≤ 6, and prostate specific antigen (PSA) < 10 ng/mL) either treated with
definitive intent or untreated in active surveillance with stable disease are not
excluded
- Has known active carcinomatous meningitis. Participants with previously treated
brain metastases may participate provided they are radiologically stable, i.e.
without evidence of progression for at least 4 weeks by repeat imaging (note that
the repeat imaging should be performed during study screening), clinically stable
and without requirement of steroid treatment for at least 14 days prior to first
dose of study intervention
- Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its
excipients
- Has active autoimmune disease that has required systemic treatment in the past 2
years except replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid)
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- History of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus
(defined as detectable HCV RNA [qualitative]) infection.
Note: Testing for Hepatitis B or C is not required unless mandated by local health
authority
- Has not adequately recovered from major surgery or has ongoing surgical
complications
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality or other circumstance that might confound the results of the study,
interfere with the participant's participation for the full duration of the study,
such that it is not in the best interest of the participant to participate, in the
opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment
- Has had an allogenic tissue/solid organ transplant
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCLA / Jonsson Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Contact:
Last name:
Dana M. Chase
Phone:
877-602-4111
Email:
Dana.Chase@chw.edu
Investigator:
Last name:
Dana M. Chase
Email:
Principal Investigator
Facility:
Name:
University of California San Diego (UCSD)
Address:
City:
San Diego
Zip:
96960
Country:
United States
Contact:
Last name:
Alexandrea O. Cronin
Email:
aocronin@health.ucsd.edu
Investigator:
Last name:
Alexandrea O. Cronin
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Contact:
Last name:
Shanna Reta
Email:
Shanna-Reta@ouhsc.edu
Investigator:
Last name:
Shanna Reta
Email:
Principal Investigator
Facility:
Name:
University of Virginia Cancer Center
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Contact:
Last name:
Linda R. Duska
Email:
lduska@virginia.edu
Investigator:
Last name:
Linda R. Duska
Email:
Principal Investigator
Start date:
January 31, 2025
Completion date:
January 31, 2031
Lead sponsor:
Agency:
Jonsson Comprehensive Cancer Center
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Jonsson Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06543576
