Clinical Study of Sodium Cridanimod in Conjunction with Hormonal Therapy in Patients with Progesterone Receptor Negative Recurrent or Persistent Endometrial Carcinoma.

Conditions: PrR negative papillary serous adenocarcinoma, endometroid type of endometrial carcinoma
MedDRA version: 17.0Level: LLTClassification code 10014743Term: Endometrial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0Level: LLTClassification code 10014747Term: Endometrial carcinoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0Level: PTClassification code 10033700Term: Papillary serous endometrial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001434-29-CZ

Lead Sponsor: AS Kevelt

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: 58

Inclusion Criteria

1.Female patients age 18 and older;
2.Histologically confirmed papillary serous adenocarcinoma or endometroid type of endometrial carcinoma (histological documentation of recurrence is not required);
3.Patient has documented evidence of PrR negative endometrial cancer. PrR negativity can be determined by immunohistochemistry. The tumor is considered PrR negative if the number of PrR positive cells is less than 1% determined by immunohistochemistry;
4.Availability of tumor tissue sample that can be used for assessment of PrR levels with the use of immunohistochemistry;
5.Recurrent or persistent (after the failure of chemotherapy) disease that cannot be treated with surgery or radiotherapy;
6.Documented disease progression after a platinum based chemotherapy in patients for whom administration of taxanes and anthracyclines is not planned. Progression must fulfill one of the following criteria:
-Progression has occurred within 30 days of platinum based chemotherapy consisting of minimum of two cycles of cisplatin-based (=60 mg/m2/cycle) or carboplatin-based (=300 mg/m2/cycle, or area under the time-concentration curve =4) chemotherapy.
-Progression after neoadjuvant or adjuvant platinum based chemotherapy if the recurrence occurred while on neoadjuvant/adjuvant chemotherapy or within 6 months since the last administration of such therapy.
7.Measurable disease as defined by RECIST 1.1 criteria;
8.At least one target lesion to be used to assess response, as defined by RECIST 1.1 criteria;
9.Tumors within a previously irradiated field will be designated as non-target lesions unless progression is documented;
10.GOG performance status 0-2 (see Appendix A);
11.Glomerular filtration rate = 50 mL/min;
12.Total bilirubin normal;
13.AST = 2.5 times upper limit of normal (ULN) (= 5 times ULN for patients with liver metastases);
14.Alkaline phosphatase = 2.5 times ULN (= 5 times ULN for patients with liver metastases);
15.Albumin = 3.0 mg/dL;
16.Ability to take oral medication;
17.Ability to understand and the willingness to sign a written informed consent document.

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 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23

Exclusion Criteria

1.Evidence of histology of the tumor other than papillary serous adenocarcinoma or endometroid type of endometrial carcinoma or mixed histology of the tumor;
2.History of hormonal therapy for endometrial carcinoma for more than 3 months;
3.History of use of progestins for a period of longer than 3 months for any indication, including endometriosis;
4.Concurrent maintenance corticosteroids;
5.Concurrent oral contraceptives/ Fertile patients must use effective barrier contraception;
6.Pregnancy as determined by pregnancy test or nursing;
7.History of bleeding (i.e. disseminated intravascular coagulation or clotting factor deficiency);
8.Prior major surgery less than 4 weeks prior to the start of the study;
9.Concurrent serious illness which, in the opinion of the investigator, would place the patient at unreasonable risk from study therapy;
10.Previous malignancy less than 3 years ago other than in situ carcinoma of the cervix, basal cell carcinoma or squamous carcinoma of the skin;
11.History of allergic reactions or idiosyncrasy attributed to progestins or compounds of similar chemical structure to sodium cridanimod or lidocaine;
12.Known brain metastases;
13.Other concurrent investigational agents;
14.Other concurrent anticancer therapies.
15.Known carrier of HIV.
16.Participation in any clinical study within 4 weeks prior to the planned administration of the drug.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess antitumor activity of sodium cridanimod in conjunction with progestin therapy as measured by objective response rate (partial and complete) in women with progestin receptor (PrR) negative recurrent or persistent endometrial carcinoma not amenable to treat with surgery, radiotherapy, chemotherapy.;Secondary Objective: - Efficacy: To assess progression free survival, time to response, time to progression, duration of overall survival and overall Disease Control Rate for patients receiving sodium cridanimod and progestin therapy.<br>- Safety: To evaluate the safety and tolerability of sodium cridanimod in conjunction with progestin therapy as measured by adverse events, laboratory safety parameters and electrocardiac safety assessments (including QT prolongation potential).<br>;Primary end point(s): Objective response rate (CR and PR) as defined by RECIST 1.1 criteria.;Timepoint(s) of evaluation of this end point: as defined by RECIST 1.1 criteria

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Progression-Free Survival (PFS). <br>Time to response <br>Duration of overall response <br>Duration of stable disease <br>Overall survival. <br>Overall Disease Control Rate <br>;Timepoint(s) of evaluation of this end point: Progression-Free Survival (PFS). The PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. <br>Time to response (The duration of time from start of treatment to CR or PR).<br>Duration of overall response (Defined in protocol appendix B).<br>Duration of stable disease (Defined in protocol appendix B).<br>Overall survival. Overall survival is defined as the period from registration onto the study until the patient’s death on any cause or the patient was last contacted.<br>Overall Disease Control Rate (Rate of patients that achieved complete response, partial response and stable disease as defined in protocol appendix B).<br>

Related Trials