A clinical trial to look at how well atezolizumab plus chemotherapy works in women with endometrial cancer

Atezolizumab Trial in Endometrial Cancer - AtTEnd

  • Endometrial Cancer
Trial Status:

Recruiting

This trial runs in
Countries
  • Italy
  • Japan
  • United Kingdom
  • Spain
  • New Zealand
  • Australia
  • Switzerland
  • South Korea
  • Germany
  • Taiwan
  • Austria
Trial Identifier:

NCT03603184 IRFMN-EN-7556

      Show trial locations

      The source of the below information is the publicly available website ClinicalTrials.gov. It has been summarised and edited into simpler language.

      The below information is taken directly from the publicly available website ClinicalTrials.gov and has not been edited.

      Results Disclaimer

      Trial Summary

      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.

      Mario Negri Institute for Pharmacological Research Sponsor
      Phase 3 Phase
      NCT03603184, IRFMN-EN-7556 Trial Identifier
      Female Gender
      ≥18 Years Age
      No Healthy Volunteers

      How does the AtTEnd clinical trial work?
      This clinical trial is recruiting women who have a particular type of cancer called endometrial cancer. In order to take part, patients must have endometrial cancer that has not been completely treated with surgery (known as residual disease) or have endometrial cancer that has previously been treated, but has now come back (known as recurrent disease).

      The purpose of this clinical trial is to compare the effects, good or bad, of atezolizumab plus chemotherapy versus placebo plus chemotherapy in patients with endometrial cancer.  In this clinical trial, you will get either atezolizumab plus chemotherapy (paclitaxel and carboplatin) or placebo plus chemotherapy (paclitaxel and carboplatin). The combination of paclitaxel and carboplatin is the current standard treatment for patients with advanced endometrial cancer.

      This is a ‘placebo-controlled’ clinical trial, which means that one of the groups will be given medicine with no active ingredients (also known as a ‘placebo’). A placebo is used to show that the doctor or the patients do not sway the results of the clinical trial.

      Neither you nor your clinical trial doctor can choose or know the group you are in. However, your clinical trial doctor can find out which group you are in, if your safety is at risk.

      How do I take part in this clinical trial?
      To be able to take part in this clinical trial, you must have been recently diagnosed with advanced endometrial cancer and not have previously received any chemotherapy treatment for advanced cancer.

      You must not have had major surgery within 1 month of you joining the trial and you cannot join the trial if you are pregnant or breastfeeding.

      If you think this clinical trial may be suitable for you and would like to take part, please talk to your doctor. If your doctor thinks that you might be able to take part in this clinical trial, he/she may refer you to the closest clinical trial doctor. They will give you all the information you need to make your decision about taking part in the clinical trial. You can also find the clinical trial locations on this page.

      You will have some further tests to make sure you will be able to take the treatments given in this clinical trial. Some of these tests or procedures may be part of your regular medical care. They may be done even if you do not take part in the clinical trial. If you have had some of the tests recently, they may not need to be done again.

      Before starting the clinical trial, you will be told about any risks and benefits of taking part in the trial. You will also be told what other treatments are available so that you may decide if you still want to take part.

      While taking part in the clinical trial,  if you are not currently pregnant but can become pregnant, you will need to either not have heterosexual intercourse or take contraceptive medication for safety reasons.

      What treatment will I be given if I join this clinical trial?
      Everyone who joins this clinical trial will be split into 2 groups randomly (like flipping a coin) and given either:

      • atezolizumab given as an infusion into your vein every 3 weeks until your disease is under control plus chemotherapy given as an infusion into your vein every 3 weeks for the first 4 to 6 months
      • OR placebo given as an infusion into your vein every 3 weeks until your disease is under control plus chemotherapy given as an infusion into your vein every 3 weeks for the first 4 to 6 months

      You will have a two in three chance of being placed in the atezolizumab group and a one in three chance of being placed in the placebo group.

      How often will I be seen in follow-up appointments, and for how long?
      You will be given the clinical trial treatment (atezolizumab or placebo) for as long as it can help you. You are free to stop this treatment at any time. After being given treatment, you will be seen by the clinical trial doctor within 1 month, then every 3 months during the first year and every 6 months thereafter. These hospital visits will include checks to see how you are responding to the treatment and any side effects that you may be having.

      What happens if I am unable to take part in this clinical trial?
      If this clinical trial is not suitable for you, you will not be able to take part. Your doctor will suggest other clinical trials that you may be able to take part in or other treatments that you can be given. You will not lose access to any of your regular care.

      For more information about this clinical trial see the For Expert tab on the specific ForPatient page or follow this link to ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03603184

      Trial-identifier: NCT03603184

      Trial Summary

      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.

      Mario Negri Institute for Pharmacological Research Sponsor
      Phase 3 Phase
      NCT03603184, IRFMN-EN-7556 Trial Identifier
      Atezolizumab, Placebos, Paclitaxel, Carboplatin Treatments
      Endometrial Cancer Condition
      Official Title

      Phase III Double-blind Randomized Placebo Controlled Trial of Atezolizumab in Combination With Paclitaxel and Carboplatin in Women With Advanced/Recurrent Endometrial Cancer

      Eligibility Criteria

      Female Gender
      ≥18 Years Age
      No Healthy Volunteers
      Inclusion Criteria

      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 :

      1. Haemoglobin ≥ 10.0 g/dL.
      2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
      3. Platelet count ≥ 100 x 109/L.
      4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
      5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN.
      6. Serum creatinine ≤ 1.5 x institutional ULN
      Exclusion Criteria

      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 .

      1. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive total hepatitis B core antibody [HBcAb]) are eligible only if hepatitis B virus (HBV) DNA is negative. The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
      2. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.

       

      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:

      1. Myocardial infarction or unstable angina within ≤ 6 months of randomization,
      2. New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF),
      3. Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled atrial fibrillation are eligible),
      4. Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with activities of daily living [ADL] requiring repair or revision) E-16. Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.

       

      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

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