A phase II clinical trial of avelumab in combination with pegylated liposomal doxorubicin in recurrent/metastatic endometrial cancer
- Conditions
- recurrent/metastatic endometrial cancerMedDRA version: 20.0Level: PTClassification code 10014734Term: Endometrial cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10014736Term: Endometrial cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10014741Term: Endometrial cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000843-14-ES
- Lead Sponsor
- GEICO (Grupo Español de Investigación en Cáncer de Ovario)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 48
1.Be willing and able to provide written informed consent/assent for the trial.
2.Be at least 18 years of age on day of signing informed consent.
3.Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) endometrial carcinoma that is incurable. All epithelial endometrial histologies are eligible including: endometrioid, serous, clear-cell carcinoma or squamous. Sarcomas and mesenchymal tumors are excluded.
4.Received only 1 prior line of systemic platinum-based treatment based chemotherapy for advanced, recurrent or metastatic endometrial cancer.
5.Have measurable disease based on RECIST 1.1, (See Appendix 3)
6.Availability of fresh or archival FFPE tumor specimens for analysis for biomarker analysis from a tumor lesion not previously irradiated.
7.ECOG Performance Status (PS) 0 or 1.
8.Demonstrate adequate organ function as defined by the following criteria:
Hematologic: Absolute neutrophil count (ANC) = 1.5 × 109/L, platelet count = 100 × 109/L, and hemoglobin = 9 g/dL (without recent transfusion)
Hepatic: Total bilirubin level = 1.5 × the upper limit of normal (ULN) range and AST and ALT levels = 2.5 × ULN or AST and ALT levels = 5 x ULN (for subjects with documented metastatic disease to the liver).
Renal: Estimated creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
9.Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Patients of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 4.3.1 – Contraception, for the course of the study through 60 days after the last dose of study medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34
1.Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
2.Receipt of 2 or more prior chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer
3.History of Clinically significant: cardiovascular disease: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication.
4.Impaired cardiac function defined as left ventricular ejection fraction (LVEF) < 50 % (or below the study site’s lower limit of normal) as measured by MUGA or ECHO or planned concomitant use of potentially cardiotoxic medication.
5.Previous anthracycline-based chemotherapy.
6.Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
7.Concurrent anticancer treatment within 28 days prior to study entry. 8.Has a known history of tuberculosis.
9.Prior organ transplantation including allogenic stem-cell transplantation.
10.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
11.Known additional malignancy diagnosed within 5 years prior to registration. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
12.Active central nervous system (CNS) metastases and/or carcinomatous meningitis. 13.Active infection requiring systemic therapy.
14.Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
15.Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
16.Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
17.Has previously participated in any other avelumab trial, or received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or any other immune-modulating mAb (including ipilimumab and any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
18.Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
19.Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
20.Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 not constituting a safety risk based on investigator’s judgment are acceptable.
21.Has received a live vaccine within 4 weeks of planned start of study therapy.
22.Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
23.Other severe acute or chronic medical or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, or l
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method