Brief Title
Carboplatin, Paclitaxel With or Without Avelumab in Advanced or Recurrent Endometrial Cancer
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
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
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
progression free survival
Secondary Outcome
overall survival
Condition
Endometrial Cancer
Intervention
Carboplatin
Study Arms / Comparison Groups
Chemotherapy
Description: Carboplatin AUC 5+Paclitaxel 175 mg/m2 q 21days for 6-8 cycles and Avelumab
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
125
Start Date
April 1, 2018
Completion Date
December 2023
Primary Completion Date
February 2023
Eligibility 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.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Sandro Pignata, M.D., Ph.D., ,
Location Countries
Italy
Location Countries
Italy
Administrative Informations
NCT ID
NCT03503786
Organization ID
MITO END-3
Secondary IDs
2016-004403-31
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute, Naples
Study Sponsor
Sandro Pignata, M.D., Ph.D., Principal Investigator, National Cancer Institute, Naples
Verification Date
May 2021