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Carboplatin, Paclitaxel With or Without Avelumab in Advanced or Recurrent Endometrial Cancer (MITO END-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03503786
Recruitment Status : Not yet recruiting
First Posted : April 20, 2018
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute, Naples

Brief Summary:
This study aims to evaluate the safety and activity of the Avelumab in combination with Carboplatin-Paclitaxel in advanced or recurrent endometrial cancer

Condition or disease Intervention/treatment Phase
Endometrial Cancer Drug: Carboplatin Drug: Paclitaxel Drug: Avelumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase 2 randomized with a safety run-in cohort for the experimental arm
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MITO END-3: A Randomized Phase II Trial of Carboplatin+Paclitaxel Compared to Carboplatin+Paclitaxel+Avelumab in Advanced (Stage III-IV) or Recurrent Endometrial Cancer
Estimated Study Start Date : April 2018
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A
Carboplatin AUC 5+Paclitaxel 175 mg/m2 q 21days for 6-8 cycles and Avelumab
Drug: Carboplatin
Carboplatin AUC 5 i.v. every 3 weeks for 6 - 8 cycles

Drug: Paclitaxel
Paclitaxel 175 mg/m2 i.v. every 3 weeks for 6-8 cycles

Experimental: Arm B
Carboplatin AUC 5+ Paclitaxel 175 mg/ m2+Avelumab 10 mg/kg q 21days for 6 -8 cycles + Avelumab 10 mg/kg every 14 days until disease progression or unacceptable toxicity
Drug: Carboplatin
Carboplatin AUC 5 i.v. every 3 weeks for 6 - 8 cycles

Drug: Paclitaxel
Paclitaxel 175 mg/m2 i.v. every 3 weeks for 6-8 cycles

Drug: Avelumab
Avelumab 10 mg/kg every 3 weeks for 6-8 cycles + Avelumab 10 mg/kg every 14 days until disease progression or unacceptable toxicity




Primary Outcome Measures :
  1. progression free survival [ Time Frame: 18 months from beginning of treatment ]

Secondary Outcome Measures :
  1. overall survival [ Time Frame: 3 years ]
  2. number of patients with complete and partial responses [ Time Frame: 18 months ]
  3. worst grade toxicity per patient [ Time Frame: evaluated every 3 weeks up to 2 years ]
    according to Common Toxicity Criteria for Adverse Events v. 4.03

  4. changes in patient-reported outcome (PRO) scores of quality of life and disease-related symptoms from baseline [ Time Frame: up to 2 years ]
    EORTC QOL questionnaire

  5. changes in patient-reported outcome (PRO) scores of symptomatic toxicities during treatment [ Time Frame: up to 2 years ]
    PRO-CTCAE questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female aged at least 18 years on day of signing informed consent
  2. ECOG Performance Status of 0-1
  3. Patients with newly diagnosed or recurrent endometrial cancer FIGO stage III-IV and histologically-confirmed (any histology except sarcoma and carcinosarcoma)
  4. Patients may have received adjuvant treatment (platinum-based cytotoxic chemotherapy and/or radiotherapy). Patients having received prior chemotherapy must have completed their treatment at least 6 months prior to registration for protocol therapy. Patients having received prior radiotherapy must have completed their treatment at least 28 days prior to registration for protocol therapy
  5. Have measurable disease based on RECIST v1.1 criteria
  6. Availability of tumor samples for biomarker analysis
  7. Endometrial cancer will include all carcinomas, including endometrioid carcinoma, papillary serous carcinoma, clear cell carcinoma
  8. Adequate hematological function defined by absolute neutrophil count (ANC) ≥ 1500 × mm3, platelet count ≥ 100,000 × mm3, and hemoglobin ≥ 9 g/dL (may have been transfused)
  9. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN for all subjects (or ≤ 5 x ULN if liver metastases are present)
  10. Adequate renal function defined by an estimated creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault formula or serum creatinine ≤ 1.5 ULN (for local institutional standard method)
  11. Alkaline phosphatase < 1.5 x ULN for the institution (if > 1.5 x ULN, then alkaline phosphatase liver fraction must be < 1.5 ULN)
  12. Be willing and able to provide written informed consent/assent for the trial
  13. Females of childbearing potential must have a negative serum pregnancy test (serum hCG) at screening. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for ≥1 year
  14. Highly effective contraception for females if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year). Highly effective contraception is required at least 28 days prior, throughout and for at least 60 days after Avelumab treatment

Exclusion Criteria:

  1. Women who are pregnant or lactating
  2. Patients with brain metastases, except those meeting the following criteria:

    • Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
    • No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
    • patients must be either off steroids or on a stable or decreasing dose of <10mg daily prednisone (or equivalent)
  3. Prior Anticancer treatment for advanced disease and/or prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Previous hormonal therapy for advanced disease is allowed, but treatment must be discontinued at least 28 days prior to registration for protocol therapy
  4. History of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
  5. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
  6. Prior organ transplantation, including allogeneic stem cell transplantation
  7. Significant acute or chronic infections including, among others:

    • Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    • Positive test for hepatitis B surface antigen and / or confirmatory hepatitis C RNA (if anti-hepatitis C antibody tested positive)
    • Evidence of interstitial lung disease or active non-infectious pneumonitis.
    • Active infection requiring systemic therapy
    • Known history of active Tuberculosis Bacillus (TB)
  8. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:

    • Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
    • Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
    • Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
  9. Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable
  10. Another primary malignancy within the past five years (except for non-melanoma skin cancer and cervical carcinoma in situ).
  11. Concurrent treatment with immunosuppressive or investigational agents EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  12. Active cardiac disease, defined as:

    • Myocardial infarction or unstable angina pectoris within 6 months of the first date of study therapy,
    • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrio-ventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.
    • New York Heart Association (NYHA) Class III or greater congestive heart failure, or left ventricular ejection fraction of < 40%.
  13. Known alcohol or drug abuse
  14. Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
  15. Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  16. All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma) including recent or active suicidal ideation or behavior, which, in the opinion of the Investigator, may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03503786


Contacts
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Contact: Gennaro Daniele, M.D., Ph.D. +39 081 5903571 g.daniele@istitutotumori.na.it
Contact: Jane Bryce, MSN +39 081 5903571 j.bryce@istitutotumori.na.it

Locations
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Italy
Ospedale Senatore Antonio Perrino
Brindisi, Italy
Fondazione del Piemonte per l'Oncologia
Candiolo, Italy
Istituto Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Italy
IRCCS San Raffaele
Milano, Italy
Istituto Nazionale Tumori
MIlano, Italy
AOU Policlinico Federico II
Napoli, Italy
AOU Università degli studi della Campania "Luigi Vanvitelli"
Napoli, Italy
Istituto Nazionale dei Tumori
Napoli, Italy
Ospedale Silvestrini
Perugia, Italy
Ospedale S. Giovanni Calibita Fatebenefratelli
Roma, Italy
Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore
Roma, Italy
Sponsors and Collaborators
National Cancer Institute, Naples
Investigators
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Principal Investigator: Sandro Pignata, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Francesco Perrone, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Gennaro Daniele, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: Ciro Gallo, M.D. University of Campania "Luigi Vanvitelli"
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Responsible Party: National Cancer Institute, Naples
ClinicalTrials.gov Identifier: NCT03503786    
Other Study ID Numbers: MITO END-3
2016-004403-31 ( EudraCT Number )
First Posted: April 20, 2018    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Cancer Institute, Naples:
PD-L1 Expression
advanced endometrial cancer
recurrent endometrial cancer
Patient reported outcomes
Additional relevant MeSH terms:
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Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action