Atezolizumab Trial in Endometrial Cancer - AtTEnd (AtTEnd)
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|ClinicalTrials.gov Identifier: NCT03603184|
Recruitment Status : Recruiting
First Posted : July 27, 2018
Last Update Posted : November 14, 2019
|First Submitted Date ICMJE||May 21, 2018|
|First Posted Date ICMJE||July 27, 2018|
|Last Update Posted Date||November 14, 2019|
|Actual Study Start Date ICMJE||October 2, 2018|
|Estimated Primary Completion Date||July 2021 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT03603184 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Atezolizumab Trial in Endometrial Cancer - AtTEnd|
|Official Title ICMJE||Phase III Double-blind Randomized Placebo Controlled Trial of Atezolizumab in Combination With Paclitaxel and Carboplatin in Women With Advanced/Recurrent Endometrial Cancer|
Atezolizumab is an engineered humanised monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1.
In May 2016 atezolizumab was approved by the FDA for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant); in October 2016 it was approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities. Finally, in April 2017 atezolizumab was granted accelerated approval by FDA for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy. Combinations of atezolizumab with chemotherapeutic agents and/or targeted therapies were studied in different solid tumors such as melanoma, NSCLC, renal cell carcinoma and colorectal carcinoma. From these studies the AE profile of atezolizumab combinations were consistent with that of the individual agents.
Finally, preliminary results of a Phase Ia study of Atezolizumab (NCT01375842) monotherapy in relapsed endometrial cancer were reported as abstract at ASCO 2017. Fifteen patients were evaluated for safety and efficacy with a minimum follow-up of 11.2 months. No G4-5 related AEs occurred. Regarding efficacy ORR was 13% [2/15] by RECIST. Atezolizumab seemed to have a favorable safety profile, with durable clinical benefit in some patients. Further studies with atezolizumab are warranted given its promising results in advanced endometrial cancer and the limited efficacy of current treatment options.
|Detailed Description||Not Provided|
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Condition ICMJE||Endometrial Cancer|
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||July 2022|
|Estimated Primary Completion Date||July 2021 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
I-1. Newly diagnosed, histologically-confirmed with residual disease after surgery either measurable or evaluable, or inoperable stage III-IV endometrial carcinoma/carcinosarcoma, after diagnostic biopsy, and naïve to first line systemic anti-cancer treatment. Recurrent endometrial cancer patients if not yet treated for recurrent disease.
I-2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 I-3. Age ≥ 18 years I-4. Only one prior line of systemic platinum-based regimen is permitted if the platinum-free interval ≥ 6 months. Such prior line is the up-front/adjuvant treatment which can be concurrent chemoradiation or concurrent chemoradiation followed by chemotherapy or only chemotherapy.
I-5. Patients with history of primary breast cancer may be eligible provided they completed their definitive anticancer treatment more than 3 years ago and they remain breast cancer disease free prior to start of study treatment.
I-6. Previous pelvic and outside pelvis radiation is allowed if completed more than 6 weeks ago.
I-7. Signed informed consent and ability to comply with treatment and follow-up.
I-8. Representative FFPE tumor sample or, only if unfeasible, at least 20 unstained slides from initial surgery or from diagnostic biopsy, in case surgery was not performed, available and sent to central laboratory for Micro Satellite (MS) determination prior to randomization.
I-9. Patients must have normal organ and bone marrow function :
E-1. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast. Patients with a history of localized malignancy diagnosed over 5 years ago may be eligible provided they completed their adjuvant systemic therapy prior to randomization and that the patient remains free of recurrent or metastatic disease.
E-2. Patients with uterine leiomyosarcoma . E-3. Major surgery within 4 weeks of starting study treatment or patients who have not completely recovered from the effects of any major surgery.
E-4. Previous allogeneic bone marrow transplant or previous solid organ transplantation.
E-5. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted).
E-6. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti−PD1, or anti−PDL1 therapeutic antibodies or anti-CTLA4 .
E-7. Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1.
E-8. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial. However, please note that the use of inhaled corticosteroids for chronic obstructive pulmonary disease or for asthma is allowed, as well as the use of mineralocorticoids (e.g., fludrocortisones) and low-dose supplemental corticosteroids for adrenocortical insufficiency and for patients with orthostatic hypotension. The use of corticosteroids as premedication for paclitaxel-based regimen is allowed).
E-9. History of autoimmune disease, including but not limited to myasthenia gravis, myositis,autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis [please note: patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible; patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible; history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia) is permitted].
E-10. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
E-11. Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C .
E-12. Active tuberculosis (all patients will have tuberculin [PPD] skin test or Interferon-Gamma Releasing Assay [IGRA] done locally prior to inclusion to study) E-13. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 E-14. Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (example approximately October to March in the Northern Hemisphere). Patients must not receive live, attenuated influenza vaccine.
E-15. Clinically significant (e.g. active) cardiovascular disease, including:
E-17. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in any case of suspected central nervous system (CNS) involvement .
E-18. History or evidence upon neurological examination of central nervous system (CNS) disease, unless asymptomatic and adequately treated with standard medical therapy.
E-19. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment related complications.
E-20. Women of childbearing potential (<2 years after last menstruation) not willing to use highly-effective means of contraception.
E-21. Pregnant or lactating women. E-22. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
E-23. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation.
E-24. Known hypersensitivity reaction or allergy to drugs chemically related to carboplatin, paclitaxel, or their excipients that contraindicates the subject's participation
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||Austria, Germany, Italy, Japan, Spain, Switzerland, United Kingdom|
|Removed Location Countries|
|NCT Number ICMJE||NCT03603184|
|Other Study ID Numbers ICMJE||IRFMN-EN-7556|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Mario Negri Institute for Pharmacological Research|
|Study Sponsor ICMJE||Mario Negri Institute for Pharmacological Research|
|Collaborators ICMJE||Not Provided|
|PRS Account||Mario Negri Institute for Pharmacological Research|
|Verification Date||November 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP