Trial Assessing the Inhibitor of Programmed Cell Death Ligand 1 (PD-L1) Immune Checkpoint Atezolizumab

NCT03612791 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 2017-003622-332017/2608
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this randomized phase II trial is to evaluate the clinical benefits of the addition of atezolizumab to standard chemoradiotherapy (CRT) (first given concurrently with CRT, then continued as adjuvant treatment), compared with CRT alone, on investigator-assessed progression-free survival (PFS), as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

Conditions

Locally Advanced Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  The primary endpoint is progression free survival (PFS), defined as the time from randomization to the first documented occurrence of disease progression

  from randomization to the first documented occurrence of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurs first, up to 24 months

Study Arms (2)

Standard Treatment Arm

ACTIVE COMPARATOR

Radiotherapy (RT): * Pelvic +/- para-aortic EBRT (IMRT): 45 Gy in 25 fractions over 5 weeks (Weeks 1-5, with simultaneously integrated boosts to macroscopically involved lymph nodes, if any, in order to deliver a total dose of 60 Gy to macroscopic lymph nodes (including the dose delivered by brachytherapy). * Uterovaginal brachytherapy (Week 7; maximum interval between EBRT and brachytherapy: 14 days). If appropriate and feasible, dose escalation will be assumed, particularly for advanced disease, with the objective to deliver a minimal total dose of 85 Gy (equivalent dose in 2-Gy fractions with α/β=10 Gy) to 80% of the High Risk-Clinical Target Volume (HR-CTV), including 45 Gy through EBRT. The total dose might be lower in case of close proximity to organs at risk (OARs). * Total duration of RT (including brachytherapy) should be ≤ 55 days. Chemotherapy: \- Cisplatin infused 40 mg/m2 (maximum 70 mg) weekly IV during EBRT (Weeks 1-5).

Radiation: Radiotherapy; Drug: Cisplatin

Experimental Treatment Arm

EXPERIMENTAL

* Same treatment as described above (CRT, followed by uterovaginal brachytherapy), plus * atezolizumab administered IV 1200 mg Q3W, starting on the same week as EBRT (Week 1) and continued as an adjuvant for a total maximum of 20 cycles (approximately 14 months total of treatment).

Drug: Atezolizumab; Radiation: Radiotherapy; Drug: Cisplatin

Interventions

Atezolizumab DRUG

atezolizumab administered IV 1200 mg Q3W, starting one week before EBRT (Week -1) and continued as an adjuvant for a total maximum of 20 cycles.

Experimental Treatment Arm

Radiotherapy RADIATION

* Pelvic +/- para-aortic EBRT (IMRT): 45 Gy in 25 fractions over 5 weeks (Weeks 1-5, with simultaneously integrated boosts to macroscopically involved lymph nodes, if any, in order to deliver a total dose of 60 Gy to macroscopic lymph nodes (including the dose delivered by brachytherapy). * Uterovaginal brachytherapy (Week 7; maximum interval between EBRT and brachytherapy: 14 days). If appropriate and feasible, dose escalation will be assumed, particularly for advanced disease, with the objective to deliver a total dose of 85 Gy (equivalent dose in 2-Gy fractions with α/β=10 Gy) to 80% of the High Risk-Clinical Target Volume (HR-CTV), including 45 Gy through EBRT. The total dose might be lower in case of close proximity to organs at risk (OARs). * Total duration of RT (including brachytherapy) should be ≤ 55 days.

Experimental Treatment Arm; Standard Treatment Arm

Cisplatin DRUG

* Cisplatin infused 40 mg/m2 (maximum 70 mg) weekly IV during EBRT (Weeks 1-5). * Not administered: during the interval between EBRT and brachytherapy, or during brachytherapy, or if radiotherapy is interrupted.

Experimental Treatment Arm; Standard Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Signed informed consent (after informing the patient).
• Age ≥18 years old. Patients above 70 years old will be screened according to the G-8 screening tool. If required (G-8 score ≤14), a consultation with an onco-geriatrician will be held in order to confirm the patient eligibility
• Histologically confirmed cancer of the uterine cervix: squamous cell carcinoma (SCC), adenocarcinoma, or adenosquamous carcinoma.
• At least one evaluable lesion according to RECIST v1.1 criteria for the assessment of the principal judgment criteria. At baseline, lesion(s) must be ≥10 mm in the longest diameter (except lymp nodes which must have a short axis ≥15 mm).
• International Federation of Gynecology and Obstetrics (FIGO 2009) classification (confirmed by both clinical staging and/or imaging):
• (i) stage IB1-IIA tumour with positive pelvic nodal status, as assessed by magnetic resonance imaging (MRI) and/or fluorine-18 fluorodeoxyglucose positron emission tomography (18-FDG PET)/computerised tomography (CT); (ii) stage IIB-IVA tumour, regardless of pelvic lymph node involvement; (iii) stage IVB tumours only if the metastases are limited to the paraaortic lymph nodes.
• No evidence of metastatic disease outside the para-aortic area by primary staging (including clinical examination, pelvic MRI, 18-FDG PET, +/- laparoscopic para-aortic lymph node staging).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate haematologic and end-organ function, defined by the following laboratory results obtained within 15 calendar days prior to the first study treatment:
• Absolute neutrophil count (ANC) ≥1,500/mm3 (≥1.5 x 10\^9/L) without granulocyte colony-stimulating factor (G-CSF) support.
• Total white blood cells (WBC) \>2,000/mm3 (\>2.0 x 10\^9/L) (including Polymorphonuclear neutrophils \> 1,500/mm3 or 1.5 x 10\^9/L)
• Lymphocyte count ≥500/mm3 (≥ 0.5 x 10\^9/L)
• Platelet count ≥ 100,000/mm3 (≥ 100 x 10\^9/L) without transfusion.
• Haemoglobin ≥ 9.0 g/dL (90 g/L; patients may be transfused to meet this criterion).
• International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × upper limit of normal (ULN) for patients not receiving therapeutic anticoagulation.

You may not qualify if:

• Stage IB1 and IIA cervical cancer with no regional lymph node metastases (N0).
• Stage IVB cervical cancer with presence of distant metastases other than para-aortic lymph node metastases.
• Prior surgery for cervical cancer unless cone resection and paraaortic lymphadenectomy.
• Prior pelvic radiotherapy, other radiotherapy, chemotherapy or immunotherapy.
• Any malignancy other than the disease under study in the past 5 years excepting skin cancers such as BCC or SCC.
• Pregnant or lactating women, or intending to become pregnant during the study.
• For patient ≥ 70 years old with a G-8 score ≤ 14, unconfirmation of patient eligibility done by the onco-geriatrician at screening
• History of clinically relevant cardiovascular disease, congestive heart failure (New York Heart Association \[NYHA\] Class II or greater), or a known left ventricular ejection fraction (LVEF) \<50%, symptomatic coronary artery disease, poorly controlled cardiac arrhythmia, or myocardial infarction.
• Active inflammatory bowel disease, lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome.
• Serious infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
• Treatment with another investigational therapy within 30 days prior to initiation of the study drug.
• Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the study other than for diagnosis. The following are not considered a major surgical procedure and are therefore permitted:
• (i) placement of central venous access catheter(s) (e.g., port or similar); (ii) surgical lymph node staging with no perioperative complications; (iii) placement of ureteral catheters.
• History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins.
• Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead

Study Sites (1)

Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

MeSH Terms

Interventions

atezolizumab; Radiotherapy; Cisplatin

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: August 2, 2018
• Study Start: August 13, 2018
• Primary Completion: February 26, 2024
• Study Completion: May 13, 2025
• Last Updated: June 3, 2025

Record last verified: 2025-06

Locations

FR (1)