Platinum Chemotherapy plus Paclitaxel with Bevacizumab and Atezolizumab versus Chemotherapy plus Paclitaxel and Bevacizumab in Carcinoma of the Cervix
- Conditions
- Metastatic (stage IVB), Persistent, or Recurrent Carcinoma of the CervixMedDRA version: 21.1Level: PTClassification code 10008342Term: Cervix carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000367-83-DE
- Lead Sponsor
- Grupo Español de Investigación en Cáncer de Ovario (GEICO)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 404
1. Female patients must be =18 years of age.
2. Signed informed consent before any study-specific procedure
3. Able (in the investigator´s judgment) to comply with the study protocol
4. GOG/Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
5. Life expectancy =3 months
6. Histologically- or cytologically-confirmed diagnosis of metastatic (stage IVB), persistent, or recurrent cervical cancer (histologies other than squamous cell, adenocarcinoma, or adenosquamous will be excluded) not amenable for curative treatment with surgery and/or radiation therapy. The inclusion of patients with adenocarcinoma histology will be capped to 20% of the whole study population.
7. No prior systemic anti-cancer therapy for metastatic or recurrent disease.
- Concurrent chemo-radiotherapy treatment with curative intent or adjuvant chemo-radiotherapy must have been completed =3 months (90 days) prior to enrollment.
- Palliative radiation therapy (e.g., for pain or bleeding) 6 weeks prior enrollment is allowed as long as this does not affect measurable disease and patients are recovered from its symptoms.
8. Measureable disease by RECIST v1.1 criteria: Patients must have at least 1 target lesion to be used to assess response on this protocol as defined by RECIST v1.1. If the only target lesion is limited to the radiation field, a biopsy is required to confirm malignancy.
9. A tumor specimen is mandatory at study entry. This may be an archival biopsy or, in its absence, a tumor biopsy obtained within 3 months of randomization from a non-irradiated lesion. Paired recent biopsies at baseline (lesion not previously irradiated; within 3 months of randomization) and at progression disease will not be mandatory, nevertheless they are encouraged as long as these are feasible.
10. Adequate organ function:
o Hemoglobin =9 g/dL (transfusion and / or erythropoietin permitted)
o ANC =1.5 × 109/L
o Lymphocyte count =0.5 × 109/L
o Platelet count =100 x 109/L
11. Adequate liver function:
o Serum albumin =2.5 g/dL
o Total serum bilirubin =1.5 ×ULN
o AST and ALT =2.5 × ULN or =5 × ULN if tumor involvement (liver) is present
12. Adequate renal function:
o Patients with serum creatinine <1.5 × ULN
o Urine dipstick for proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1 g of protein in 24 hours or urine protein/creatinine (UPC) ratio = 1.0
13. Adequate coagulation:
o Blood coagulation parameters (PTT, PT/INR): PT such that international normalized ratio (INR) is =1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT <1.5 ×
ULN.
14. Negative Test Results for Hepatitis
15. Toxicities related to previous treatments must be recovered to < grade 2 (with the exception of alopecia).
16. Female participants must be postmenopausal (= 12 months of non-therapyinduced amenorrhoea) or surgically sterile (absence of ovaries and/or uterus, or who received therapeutic radiation to the pelvis) or otherwise have a negative serum pregnancy test within 7 days of the first study treatment and agree to abstain from heterosexual intercourse or use single or combined contraceptive methods that result in a failure rate of <1% per year during the whole treatment period of the study and for at least 5 months (if the las
1. Disease that is suitable for local therapy administered with curative intent.
2. Prior radiotherapy delivered using cobalt.
3. Patients with Stage IVA not amendable to concurrent chemo-radiation as primary treatment.
4. Ongoing disease involving the bladder or rectum at screening/baseline.
5. Evidence of abdominal free air.
6. Bilateral hydronephrosis.
7.Patients previously treated with chemotherapy except when used concurrently with radiation therapy. Patients who have received either concurrent paclitaxel with radiation therapy or carboplatin/paclitaxel as neoadjuvant or adjuvant therapy are ineligible for the study.
8. Prior treatment with any anti-VEGF drug.
9. Patients with a concomitant malignancy other than non-melanoma skin cancer.
10. Known brain metastases or spinal cord compression.
11. History or evidence, following a neurological examination unless properly treated with standard medical treatment.
12. Patients with serious non-healing wound, ulcer, or bone fracture.
13. Acute intestinal obstruction or sub-occlusion episode in the last 6 months.
14. Active GI bleeding or GI ulcer.
15. History of Crohn's disease or inflammatory bowel disease.
16. Prior bowel resection =6 weeks preceding first study dose.
17. History of diverticulitis requiring medical intervention.
18. NCI CTCAE (version 5.0) grade =2 enteritis.
19. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to D1C1.
20. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to D1C1.
21. Patients with active bleeding or pathologic conditions that carry high risk of bleeding.
22. Current or recent chronic daily treatment with aspirin, clopidogrel, or current or recent use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes.
23. Patients with pre-existing Grade 2 or greater peripheral neuropathy.
24. History of any grade =3 venous thromboembolic event (VTE).
25. Patients with clinically significant cardiovascular disease.
26. Left ventricular ejection fraction defined by MUGA/ECHO below the institutional lower limit of normal
27. Uncontrolled tumor-related pain.
28. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
29. Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
30. History of autoimmune disease.
31. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field is permitted.
32. Active tuberculosis.
33. Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
34. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
35. Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1,Day 1.
36. Known human immunodeficiency virus (HIV).
37. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
38. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method