Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Uterine Cervical Neoplasms

Recurrence

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Paclitaxel

Albumin-Bound Paclitaxel

Bevacizumab

Carboplatin

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

On day 1 of each 21 day cycle, participants will be administered Pembrolizumab 200mg (IV); Chemotherapy including Paclitaxel 175mg/m2 or 135 mg/m2 (IV), and Cisplatin 50mg/m2 (IV) or Carboplatin AUC 5; and Bevacizumab 15mg/kg (IV).

Marilyn Huang, MD, MS

The investigators propose to evaluate the efficacy of the combination of standard chemotherapy with bevacizumab with Pembrolizumab in women with recurrent, persistent, or metastatic cervical cancer.

Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Cervical Cancer

Phase II Single Arm Study of Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

Objective response defined as the proportion of patients showing complete or partial response to study therapy. Response to therapy will be evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Rate of Progression-Free Survival (PFS) in study participants. PFS is defined as the time from start of treatment until documented disease progression or death (by any cause, in the absence of progression). In alive, progression-free patients, PFS will be censored at the last evaluable tumor assessment.

Rate of Overall Survival (OS) in study participants. OS is defined as the time from start of treatment until death due to any cause.

The safety and tolerability profile of the study therapy will be determined by the proportion of study participants experiencing treatment-related adverse events (AEs) and serious adverse events (SAEs). Treatment-related AEs and SAEs will be evaluated with respect to grade and relationship to treatment, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.

Merck Sharp & Dohme LLC

University of Miami

Disease Attributes

Immunomodulating Agents

Atezolizumab

Stereotactic body radiation therapy (SBRT) followed by atezolizumab, 1 week later.

SBRT with 24 Gy in 3 fractions to participants with ≥ 2 metastatic sites.

Stereotactic body radiation therapy (SBRT)

Atezolizumab 1200 mg intravenously (IV) every 3 weeks.

Lauren (Taylor) Michael

Kamran Ahmed, M.D.

Allison Quick, MD

Corynn Mcatee

The purpose of this study is to see if treatment with atezolizumab and stereotactic body radiation therapy (SBRT) will improve the objective response rate (ORR) compared with atezolizumab alone in patients with recurrent, persistent, or metastatic cervical cancer.

SBRT and Atezolizumab in the Management of Recurrent, Persistent, or Metastatic Cervical Cancer

Phase II Study of Stereotactic Body Radiation Therapy and Atezolizumab in the Management of Recurrent, Persistent, or Metastatic Cervical Cancer

ORR by Immune-Modified Response Evaluation Criteria in Solid Tumors (irRECIST) criteria of SBRT and atezolizumab in the management of recurrent/persistent/metastatic cervical cancer. Complete Response (CR): Disappearance of all lesions; Partial Response (PR): ≥30% decrease in tumor burden, a in the absence of CR; Progressive Disease (PD): ≥20% increase in tumor burden; Stable Disease (SD): Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.

PFS following combined modality management with SBRT and atezolizumab in the management of recurrent/persistent/metastatic cervical cancer. PFS: Time from the date of start of treatment to the investigator-determined date of progression (determined by irRECIST criteria) or death due to any cause, whichever occurs first. Progressive Disease (PD): ≥20% increase in tumor burden

OS following combined modality management with SBRT and atezolizumab in the management of recurrent/persistent/metastatic cervical cancer. OS: Time from the date of start of treatment to death.

Genentech, Inc.

H. Lee Moffitt Cancer Center and Research Institute

Carcinoma

Adenocarcinoma

Carcinoma, Squamous Cell

Carcinoma, Adenosquamous

A Phase II Study of Cabozantinib (XL 184)Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer

Cabozantinib 40 MG oral once a day

Pembrolizumab 200 mg IV every 3 weeks

Stefanie White

This study is a multi-center, single arm, open label trial to evaluate the efficacy and safety of Cabozantinib (XL184) plus Pembrolizumab in recurrent, persistent and/or metastatic cervical cancer with PD-L1 tumor positivity.

Cabozantinib Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer

A Phase II Study of Cabozantinib (XL184) Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer

Six months progression free survival as defined by RECIST v1.1 measured from signed written consent to the date of first documented tumor progression using RECIST v1.1, or death due to any cause or 24 months after the end of study treatment.

Overall response defined by Response Evaluation Criteria in Solid Tumors (RECIST v.1.1 criteria).

Overall survival will be defined as the time from signed written consent to the date of death or 24 months after the end of study treatment. A patient who has not died will be censored at the last known date of contact

Evaluate the safety and tolerability measured by incidence of adverse events and serious adverse events, deaths, and laboratory abnormalities as measured by Common Terminology Criteria for Adverse Events v.4.0

Quality of life as assessed by FACT Cx quality of life questionnaire. This frequency questionnaire is scaled from 0-4 with 0 being not at all and 4 being very much.

Exelixis

University of South Alabama

Vaccines

Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.

Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.

1.1 mL intramuscular (IM) injection of INO-3112 (VGX-3100 + INO-9012) was administered followed immediately by electroporation (EP) with CELLECTRA™-5P on Day 0, Week 4, Week 8, and Week 12.

INO-3112

CELLECTRA™-5P was used for EP following IM delivery of INO-3112 on Day 0, Week 4, Week 8, and Week 12.

CELLECTRA™-5P

Jeffrey Skolnik, MD

This is an open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 DNA vaccines delivered by electroporation (EP) to female participants with HPV-16 and/or 18-positive cervical carcinoma.

This is a Phase I/IIa, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 \[VGX-3100 and INO-9012\] delivered intramuscularly by electroporation in approximately 30 female participants with biopsy-proven, Stage IB-IVB inoperable invasive cervical carcinoma associated with HPV 16 and/or 18 who have completed treatment with standard chemoradiation therapy with curative intent (Cohort I) or in participants with persistent and/or recurrent cervical cancer associated with HPV 16 and/or 18 following salvage therapy (Cohort II).

Only female participants with biopsy-proven, Stage IB-IVB inoperable invasive cervical carcinoma associated with HPV-16 and/or HPV-18 were included.

A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer

Phase I/IIA, Open-Label, Safety, Tolerability, and Immunogenicity Study of INO-3112 Delivered by Electroporation (EP) in Women With Cervical Cancer After Chemoradiation for Newly Diagnosed Disease or Therapy for Recurrent and/or Persistent Disease

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug.

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug. The severity of TEAEs was assessed by the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE,v 4.03). TEAEs were graded on a 5-point scale where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Potentially life-threatening and 5 = Death.

Injection site reactions and administration site pain were evaluated starting 30 minutes following injection/EP. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' (Food and Drug Administration \[FDA\] Guidance for Industry, September 2007). Local reaction to the injectable product such as pain, tenderness, erythema/redness and induration/swelling were graded on a 4-point scale where: 1 = Mild, 2 = Moderate, 3 = Severe and 4 = Potentially life-threatening.

Clinical laboratory parameters (hematology, serum chemistry, and creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Hematology parameters analyzed for this outcome measure included: white blood cell (WBC) count, count of lymphocytes (L), monocytes (M) and neutrophils (N).

Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Clinical chemistry parameter assessed in this outcome measure included alkaline phosphatase (ALP), alanine amino transferase (ALT) and aspartate amino transferase (AST).

Whole blood and serum samples to be tested for antibodies to the human papillomavirus (HPV) E6 and E7 proteins and/or T-lymphocytes producing interferon-gamma (IFN-γ) elicited by INO-3112 were assessed by enzyme-linked immunosorbent spot-forming assay (ELISpot).

Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components.

Inovio Pharmaceuticals

Cohort I: INO-3112: Curative Intent

Cohort II: INO-3112: Salvage Therapy

Total

Age, Continuous

Female

Sex/Gender, Customized

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study Director

Safety population included all participants who received at least one dose of study treatment plus EP.

Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)

Anaemia

Disseminated Intravascular Coagulation

Abdominal Pain

Intestinal Perforation

Pneumonia

Pathological Fracture

Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03)

Injection Site Bruising

Injection Site Discolouration

Injection Site Erythema

Injection Site Haemorrhage

Injection Site Pain

Injection Site Swelling

Percentage of Participants With Injection Site Reactions

The above-mentioned outcome could not be assessed as no data were captured that reflect the expected rates of acute gastrointestinal, genitourinary or other chemoradiation side effects, in order to compare those collected on this study with those from prior studies. While adverse event data related to study therapy were captured, these were not graded per acute radiation morbidity score because of the above-noted limitation. No comparison was thus possible that would reflect rates expected.

Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria

Baseline

Change from Baseline at Week 4

Change from Baseline at Week 8

Change from Baseline at Week 12

Change from Baseline at Week 16

Change from Baseline at Week 24

Change from Baseline at Week 32

Change from Baseline at Week 48

Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.

Change From Baseline in Hematocrit at the Indicated Time Points

The safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.

Change From Baseline in Hemoglobin at the Indicated Time Points

L, Baseline

L,Change from Baseline at Week 4

L,Change from Baseline at Week 8

L, Change from Baseline at Week 12

L, Change from Baseline at Week 16

L, Change From Baseline at Week 24

L, Change from Baseline at Week 32

L, Change from Baseline at Week 48

M, Baseline

M,Change from Baseline at Week 4

M,Change from Baseline at Week 8

M,Change from Baseline at Week 12

M,Change from Baseline at Week 16

M,Change from Baseline at Week 24

M,Change from Baseline at Week 32

M,Change from Baseline at Week 48

N, Baseline

N,Change from Baseline at Week 4

N,Change from Baseline at Week 8

N,Change from Baseline at Week 12

N,Change from Baseline at Week 16

N,Change from Baseline at Week 24

N,Change from Baseline at Week 32

N,Change from Baseline at Week 48

WBC, Baseline

WBC, Change from Baseline at Week 4

WBC, Change from Baseline at Week 8

WBC, Change from Baseline at Week 12

WBC, Change from Baseline at Week 16

WBC, Change from Baseline at Week 24

WBC, Change from Baseline at Week 32

WBC, Change from Baseline at Week 48

Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points

Platelet Count, Baseline

Platelet Count, Change from Baseline at Week 4

Platelet Count, Change from Baseline at Week 8

Platelet Count, Change from Baseline at Week 12

Platelet Count, Change from Baseline at Week 16

Platelet Count, Change From Baseline at Week 24

Platelet Count, Change from Baseline at Week 32

Platelet Count, Change from Baseline at Week 48

Change From Baseline in Platelet Count at the Indicated Time Points

RBC Count, Baseline

RBC Count, Change from Baseline at Week 4

RBC Count, Change from Baseline at Week 8

Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points

ALP, Baseline

ALP, Change from Baseline at Week 4

ALP, Change from Baseline at Week 8

ALP, Change from Baseline at Week 12

ALP, Change from Baseline at Week 16

ALT, Baseline

ALT, Change from Baseline at Week 4

ALT, Change from Baseline at Week 8

ALT, Change from Baseline at Week 12

ALT, Change from Baseline at Week 16

AST, Baseline

AST, Change from Baseline at Week 4

AST, Change from Baseline at Week 8

AST, Change from Baseline at Week 12

Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Cervical Cancer	NCT03367871	Cervical Cancer	Pembrolizumab Paclitaxel Cisplatin Carboplatin Bevacizumab	18 Years -	University of Miami
SBRT and Atezolizumab in the Management of Recurrent, Persistent, or Metastatic Cervical Cancer	NCT03614949	Cervical Cancer Cervical Cancer... Cervical Cancer...	Stereotactic bo... Atezolizumab	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Cabozantinib Plus Pembrolizumab for Recurrent, Persistent and/or Metastatic Cervical Cancer	NCT04230954	Cervical Cancer Recurrent Cervi... Metastatic Cerv... Persistent Cerv...	Cabozantinib 40... Pembrolizumab 2...	18 Years -	University of South Alabama
A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer	NCT02172911	Cervical Cancer	INO-3112 CELLECTRA™-5P	18 Years -	Inovio Pharmaceuticals
Phase II Study of Pazopanib and Topotecan in Cervical Cancer	NCT02348398	Cervical Cancer	Pazopanib Topotecan Phone Call	18 Years -	M.D. Anderson Cancer Center
First-line Treatment With Camrelizumab + Apatinib Versus Chemotherapy + Bevacizumab in Advanced Cervical Cancer	NCT04974944	Stage IVB Cervi... Recurrent Cervi... Persistent Cerv...	Camrelizumab Apatinib Paclitaxel Cisplatin Carboplatin Bevacizumab	18 Years - 70 Years	Sun Yat-sen University
A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer	NCT02172911	Cervical Cancer	INO-3112 CELLECTRA™-5P	18 Years -	Inovio Pharmaceuticals
Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Cervical Cancer	NCT03367871	Cervical Cancer	Pembrolizumab Paclitaxel Cisplatin Carboplatin Bevacizumab	18 Years -	University of Miami
First-line Treatment With Camrelizumab + Apatinib Versus Chemotherapy + Bevacizumab in Advanced Cervical Cancer	NCT04974944	Stage IVB Cervi... Recurrent Cervi... Persistent Cerv...	Camrelizumab Apatinib Paclitaxel Cisplatin Carboplatin Bevacizumab	18 Years - 70 Years	Sun Yat-sen University
SBRT and Atezolizumab in the Management of Recurrent, Persistent, or Metastatic Cervical Cancer	NCT03614949	Cervical Cancer Cervical Cancer... Cervical Cancer...	Stereotactic bo... Atezolizumab	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for persistent cervical cancer