Phase 1
Completed N=40
Atezolizumab Before and/or With Chemoradiotherapy in Immune System Activation in Patients With Node Positive Stage IB2, II, IIIB, or IVA Cervical Cancer
Source: ClinicalTrials.gov NCT03738228 ↗Enrolled (actual)
40
Serious AEs
36.1%
Results posted
Jul 2023
Primary outcomePrimary: Immune Response — 132.7; 192.8 Total number of expanded clones
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Immune Response |
132.7; 192.8 | — |
| SECONDARY Percentage of Participants With Dose Limiting Toxicities |
0; 21.43 | — |
| SECONDARY Post-treatment 3-month PET/CT Metabolic Response |
71.4; 50 | — |
| SECONDARY Adverse Events (Grade 3 or Higher) During Treatment Period as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)5 |
4; 6; 1; 0; 2; 4 | — |
| SECONDARY T Cell Receptor (TCR) Simpson Clonality |
0.0505; 0.0448 | — |
| SECONDARY Pre-treatment PD-L1 Expression |
0.75; 0.5 | — |
| SECONDARY Disease-free Survival (DFS) at 2 Years |
68.4; 52.9 | — |
| SECONDARY T Cell Receptor (TCR) Diversity |
12118; 12237 | — |
Eligibility Criteria
Inclusion Criteria
- 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 = = 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 = = 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) = = 1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment
- Significant cardiovascular or cerebrovascular disease including:
- Uncontrolled hypertension (systolic blood pressure [SBP] >= 150; diastolic blood pressure [DBP] >= 90)
- History of myocardial infarction within 6 months
- Unstable angina
- New York Heart Association functional classification II, III or IV
- Baseline ejection fraction =< 50% as assessed by echocardiogram or multigated acquisition scan (MUGA)
- Cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 6 months
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or peripheral arterial thrombosis) within 6 months
- History of abdominal/pelvic or tracheoesophageal fistula or gastrointestinal perforation and/or abscess within 6 months prior to initiation of treatment
- If patients are of child-bearing potential and do not agree to use two forms of birth control then they are ineligible
- Patients who have had a hysterectomy or are planning to have an adjuvant hysterectomy following radiation as part of their cervical cancer treatment are ineligible
- Patients scheduled to be treated with adjuvant consolidation chemotherapy at the conclusion of their standard chemoradiation
- Pregnant women are excluded from this study because radiation therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for the 5 months (150 days) after the last dose of the study agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g. osteoporosis) is allowed
- Patients with known primary central nervous system (CNS) malignancy or CNS metastases are excluded
- Patients with a prior known history of vesicovaginal, enterovaginal or colovaginal fistula
Data sourced from ClinicalTrials.gov (NCT03738228). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.