Carboplatin, Paclitaxel With or Without Avelumab in Advanced or Recurrent Endometrial Cancer

NCT03503786 | Unknown Phase 2 DMC

• 2 other identifiers: MITO END-32016-004403-31
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 11

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

Conditions

Endometrial Cancer

Keywords

PD-L1 Expression; advanced endometrial cancer; recurrent endometrial cancer; Patient reported outcomes

Outcome Measures

Primary Outcomes (1)

• progression free survival

  18 months from beginning of treatment

Secondary Outcomes (5)

• overall survival

  3 years

• number of patients with complete and partial responses

  18 months

• worst grade toxicity per patient

  evaluated every 3 weeks up to 2 years

• changes in patient-reported outcome (PRO) scores of quality of life and endometrial cancer disease and treatment related symptoms from baseline

  up to 2 years

• changes in patient-reported outcome (PRO) scores of symptomatic toxicities during treatment

  up to 2 years

Study Arms (2)

Chemotherapy

ACTIVE COMPARATOR

Carboplatin AUC 5+Paclitaxel 175 mg/m2 q 21days for 6-8 cycles and Avelumab

Drug: Carboplatin; Drug: Paclitaxel

Chemotherapy and avelumab

EXPERIMENTAL

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; Drug: Paclitaxel; Drug: Avelumab

Interventions

Carboplatin DRUG

Carboplatin AUC 5 i.v. every 3 weeks for 6 - 8 cycles

Chemotherapy; Chemotherapy and avelumab

Paclitaxel DRUG

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

Chemotherapy; Chemotherapy and avelumab

Avelumab DRUG

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

Chemotherapy and avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female aged at least 18 years on day of signing informed consent
• ECOG Performance Status of 0-1
• Patients with newly diagnosed or recurrent endometrial cancer FIGO stage III-IV and histologically-confirmed (any histology except sarcoma and carcinosarcoma)
• 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
• Have measurable disease based on RECIST v1.1 criteria
• Availability of tumor samples for biomarker analysis
• Endometrial cancer will include all carcinomas, including endometrioid carcinoma, papillary serous carcinoma, clear cell carcinoma
• 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)
• 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)
• 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)
• Alkaline phosphatase \< 1.5 x ULN for the institution (if \> 1.5 x ULN, then alkaline phosphatase liver fraction must be \< 1.5 ULN)
• Be willing and able to provide written informed consent/assent for the trial
• 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
• 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

You may not qualify if:

• Women who are pregnant or lactating
• 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)
• 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
• History of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• 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)
• Prior organ transplantation, including allogeneic stem cell transplantation
• 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)

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (11)

Ospedale Senatore Antonio Perrino

Brindisi, Italy

Location

Fondazione del Piemonte per l'Oncologia

Candiolo, Italy

Location

Istituto Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

Location

IRCCS San Raffaele

Milan, Italy

Location

Istituto Nazionale Tumori

Milan, Italy

Location

AOU Policlinico Federico II

Napoli, Italy

Location

AOU Università degli studi della Campania "Luigi Vanvitelli"

Napoli, Italy

Location

Istituto Nazionale dei Tumori

Napoli, Italy

Location

Ospedale Silvestrini

Perugia, Italy

Location

Ospedale S. Giovanni Calibita Fatebenefratelli

Roma, Italy

Location

Policlinico Universitario Gemelli Università Cattolica del Sacro Cuore

Roma, Italy

Location

Related Publications (1)

• Pignata S, Scambia G, Schettino C, Arenare L, Pisano C, Lombardi D, De Giorgi U, Andreetta C, Cinieri S, De Angelis C, Priolo D, Casanova C, Rosati M, Greco F, Zafarana E, Schiavetto I, Mammoliti S, Cecere SC, Salutari V, Scalone S, Farolfi A, Di Napoli M, Lorusso D, Gargiulo P, Califano D, Russo D, Spina A, De Cecio R, Chiodini P, Perrone F; MITO investigators. Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2023 Mar;24(3):286-296. doi: 10.1016/S1470-2045(23)00016-5. Epub 2023 Feb 14.

  PMID: 37052965 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Carboplatin; Paclitaxel; avelumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2 randomized with a safety run-in cohort for the experimental arm

Study Record Dates

• First Submitted: April 6, 2018
• First Posted: April 20, 2018
• Study Start: April 1, 2018
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: November 13, 2023

Record last verified: 2023-03

Locations

IT (11)