Atezolizumab Before and/or With Chemoradiotherapy in Immune System Activation in Patients With Node Positive Stage IB2, II, IIIB, or IVA Cervical Cancer

NCT03738228 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: NCI-2018-02791NRG-GY017U10CA180868
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 16

Brief Summary

This phase I trial studies how well atezolizumab before and/or with standard of care chemoradiotherapy works in immune system activation in patients with stage IB2, II, IIIB, or IVA cervical cancer that has spread to the lymph nodes. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab before and/or with chemoradiotherapy may lower the chance of tumors growing or spreading.

Conditions

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB2 Cervical Cancer AJCC v8; Stage II Cervical Cancer AJCC v8; Stage IIA Cervical Cancer AJCC v8; Stage IIA1 Cervical Cancer AJCC v8; Stage IIA2 Cervical Cancer AJCC v8; Stage IIB Cervical Cancer AJCC v8; Stage IIIB Cervical Cancer AJCC v8; Stage IVA Cervical Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Immune Response

  The immune response is measured by total T cell receptor beta (TCRB) clonal expansion in peripheral blood at day 21 from baseline using Adaptive Biotechnologies' immunoSEQ platform from Day -21 to Day 21 for group 1 (i.e., Arm A), and from Day 0 to Day 21 for group 2 (i.e., Arm B). The higher number of total TCR clonal expansion indicates better immune response.

  Arm A: 42 days from the first dose of Atezolizumab Arm B: 21 days from the first dose of Atezolizumab

Secondary Outcomes (7)

• Percentage of Participants With Dose Limiting Toxicities

  Arm A: 111 days, i.e., from start of the priming dose of atezolizumab until 30 days after the completion of CRT Arm B: 90 days, i.e., from start of CRT until 30 days after the completion of CRT(Chemoradiation therapy).

• Post-treatment 3-month PET/CT Metabolic Response

  3 months after completion of study treatment

• Adverse Events (Grade 3 or Higher) During Treatment Period as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)5

  Arm A: 111 days, i.e., from start of the priming dose of atezolizumab until 30 days after the completion of CRT Arm B 90 days, i.e., from start of CRT until 30 days after the completion of CRT

• T Cell Receptor (TCR) Simpson Clonality

  Arm A: 42 days from the first dose of Atezolizumab Arm B: 21 days from the first dose of Atezolizumab

• Pre-treatment PD-L1 Expression

  Within 3 days after randomization but before start of study treatment

Study Arms (2)

Arm A (atezolizumab, standard cisplatin and radiation therapy)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on days -21, 0, and 21 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care cisplatin chemotherapy IV over 90 minutes on days 0, 7, 14, 21, 28, and 35. Beginning on day 0, patients also receive standard of care radiation therapy once daily (Monday-Friday) for a total of 25 fractions with image guided brachytherapy beginning in week 4, 5, or at the end of radiation therapy.

Drug: Atezolizumab; Radiation: Brachytherapy; Drug: Cisplatin; Radiation: Radiation Therapy

Arm B (atezolizumab, standard cisplatin and radiation therapy)

EXPERIMENTAL

Patients receive atezolizumab IV over 30-60 minutes on days 0, 21, and 42 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care cisplatin chemotherapy, radiation therapy, and image guided brachytherapy as in Arm A.

Drug: Atezolizumab; Radiation: Brachytherapy; Drug: Cisplatin; Radiation: Radiation Therapy

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Arm A (atezolizumab, standard cisplatin and radiation therapy); Arm B (atezolizumab, standard cisplatin and radiation therapy)

Brachytherapy RADIATION

Undergo standard of care image guided brachytherapy

Also known as: Brachytherapy, NOS, Internal Radiation, Internal Radiation Brachytherapy, Internal Radiation Therapy, Radiation Brachytherapy, Radiation, Internal

Arm A (atezolizumab, standard cisplatin and radiation therapy); Arm B (atezolizumab, standard cisplatin and radiation therapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm A (atezolizumab, standard cisplatin and radiation therapy); Arm B (atezolizumab, standard cisplatin and radiation therapy)

Radiation Therapy RADIATION

Undergo standard of care radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm A (atezolizumab, standard cisplatin and radiation therapy); Arm B (atezolizumab, standard cisplatin and radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed newly diagnosed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): Federation of Gynecology and Obstetrics (FIGO) clinical stages IB2/IIA with positive para-aortic nodes, or FIGO clinical stages IIB/IIIB/IVA with positive pelvic or para-aortic lymph nodes (PALN). Pelvic or PALN nodal status confirmed by PET/CT scan or fine needle biopsy or extra peritoneal biopsy or laparoscopic biopsy. The PALN must be inferior to the T12/L1 interspace
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Leukocytes \>= 2,500/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL (\> 50,000 for patients with hematologic malignancies)
• Hemoglobin \>= 8 g/dL (can be transfused with red blood cells pre-study)
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN (AST and/or ALT =\< 5 x ULN for patients with liver involvement)
• Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for patients with documented liver involvement or bone metastases)
• Creatinine clearance =\< 1.5 mg/dL to receive weekly cisplatin
• Patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for cisplatin if there is no hydronephrosis and the estimated creatinine clearance (CCr) is \>= 30 ml/min. For the purpose of estimating the CCr, the formula of Cockcroft and Gault for females should be used
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
• Patient does not have a known allergy to cisplatin or compounds of similar biologic composition
• Patient is not actively breastfeeding (or has agreed to discontinue breastfeeding before the initiation or protocol therapy)
• Thyroid-stimulating hormone (TSH) within normal limits or normal free T4 in those with abnormal TSH

You may not qualify if:

• Patients who have received prior radiation therapy to the pelvis or abdominal cavity, PALN radiation, or previous therapy of any kind for this malignancy or pelvic, PALN, or abdominal radiation for any prior malignancy
• Patients with PALN nodal metastasis above the T12/L1 interspace
• Patients who had a radical hysterectomy with positive PALNs are not eligible
• Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
• Patients previously treated with systemic anticancer therapy (e.g., chemotherapy, targeted therapy, immunotherapy) within 3 years prior to entering the study
• Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to cycle 1, day 1
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or steroids as CT scan contrast premedication) may be enrolled
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Patients requiring treatment with a RANKL inhibitor (e.g., denosumab) who cannot discontinue it before treatment with atezolizumab
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible
• Patients positive for hepatitis C virus (HCV) antibody
• History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NRG Oncology: collaborator

Study Sites (16)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Mayadev J, Zamarin D, Deng W, Lankes H, O'Cearbhaill R, Aghajanian CA, Schilder R. Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer. Int J Gynecol Cancer. 2020 May;30(5):701-704. doi: 10.1136/ijgc-2019-001012. Epub 2019 Dec 22.

  PMID: 31871115 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

atezolizumab; Brachytherapy; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Physical Phenomena

Results Point of Contact

• Title: Linda Gedeon for Wei Deng
• Organization: NRG Oncology

linda.gedeon@roswellpark.org

716-845-1169

Study Officials

• Jyoti S Mayadev

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 13, 2018
• Study Start: January 7, 2019
• Primary Completion: May 1, 2022
• Study Completion: September 12, 2025
• Last Updated: November 12, 2025
• Results First Posted: July 20, 2023

Record last verified: 2025-10

Locations

US (16)