Virexxa (Sodium Cridanimod) w/Progestin Therapy in Pts w/Progesterone Receptor Neg Recurrent/Persistent Endometrial CA

Phase 2

• Conditions: Recurrent or Persistent Endometrial Carcinoma
• Interventions: Drug: Sodium cridanimod

• Registration Number: NCT02064725
• Lead Sponsor: Kevelt AS

Brief Summary

This is an open label, multi-center, single arm phase II study. The study will investigate the efficacy of sodium cridanimod in conjunction with progestin therapy in a population of patients with recurrent or persistent PrR-negative endometrial cancer.

Detailed Description

This is an open label, multi-center, single arm phase II study. The study will investigate the efficacy of sodium cridanimod in conjunction with progestin therapy in a population of patients with recurrent or persistent PrR-negative endometrial cancer.

Eligible patients will be enrolled into the study and administered sodium cridanimod in combination progestin therapy. Objective responses will be assessed at 12 week intervals. Patients will be treated for a 12 month period, followed by an additional 12 month follow up period or to disease progression whichever occurs first.

Important objectives of the study are to investigate the effect of sodium cridanimod in conjunction with progestin therapy on the level of PrR in tumor tissue and how this correlates to efficacy. To accomplish this objective, some of the patients enrolled in the study will undergo two tumor biopsies that will allow measurement of PrR levels in the tumor tissue before the treatment and after 4 weeks of therapy.

Study Timeline

• Study First Submitted: 2014-02-14
• Study First Submitted QC: 2014-02-14
• Study First Posted: 2014-02-17
• Study Start: 2014-09
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-23
• Last Update Posted: 2017-01-24
• Primary Completion: 2018-01
• Study Completion: 2018-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 8

Inclusion Criteria

• Female patients age 18 and older;

• Histologically confirmed papillary serous adenocarcinoma or endometrioid type of endometrial carcinoma (histological documentation of recurrence is not required);

• 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;

• Availability of tumor tissue sample that can be used for assessment of PrR levels with the use of immunohistochemistry;

• Recurrent or persistent (after the failure of chemotherapy) disease that cannot be treated with surgery or radiotherapy;

• 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.

• Measurable disease as defined by RECIST 1.1 criteria;

• At least one "target lesion" to be used to assess response, as defined by RECIST 1.1 criteria;

• Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented;

• GOG performance status 0-2;

• Glomerular filtration rate ≥ 50 mL/min;

• Total bilirubin normal;

• AST ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastases);

• Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver metastases);

• Albumin ≥ 3.0 mg/dL;

• Ability to take oral medication;

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sodium cridanimod	Sodium cridanimod	Sodium cridanimod in combination with megestrol acetate or medroxyprogesterone acetate. Treatment period is 12 months; patients will be followed for another 12 month period or to disease progression whichever occurs first.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	12 months

Secondary Outcome Measures

Name	Time	Method
Time to progression	24 months
Overall survival	24 months
Overall Disease Control Rate	24 months
Progression-free survival	24 months
Time to response	12 months

Trial Locations

Locations (21)

Vitebsk Regional Clinical Oncology Dispensary; 🇧🇾 Vitebsk, Belarus

University Hospital Hradec Kralove; 🇨🇿 Hradec Kralove, Czech Republic

Sumy State University; 🇺🇦 Sumy, Ukraine

Vinnitsa Regional Clinical Oncology Center; 🇺🇦 Vinnitsa, Ukraine

N.N. Alexandrov National Cancer Centre of Belarus; 🇧🇾 Minsk, Belarus

Masaryk Memorial Cancer Institute; 🇨🇿 Brno, Czech Republic

Oncology Institute of Saint Alzbeta; 🇸🇰 Bratislava, Slovakia

Poko Poprad, s.r.o.; 🇸🇰 Poprad, Slovakia

University Hospital Olomouc, Oncology; 🇨🇿 Olomouc, Czech Republic

St. Jude Hospital Yorba Linda, St. Joseph's Heritage Healthcare; 🇺🇸 Santa Rosa, California, United States

Physicians Research Group; 🇺🇸 San Jose, California, United States

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Brest Regional Clinical Hospital; 🇧🇾 Brest, Belarus

Minsk City Clinical Oncology Dispensary; 🇧🇾 Minsk, Belarus

Municipal Institution of Dnipropetrovsk Regional Rada; 🇺🇦 Dnipropetrovsk, Ukraine

University Hospital Trencin; 🇸🇰 Trencin, Slovakia

Cherkasy Regional Oncology Dispensary; 🇺🇦 Cherkasy, Ukraine

Kharkiv Regional Clinical Oncology Center; 🇺🇦 Kharkiv, Ukraine

S.P. Grigoryeva Institute of Medical Radiology; 🇺🇦 Kharkiv, Ukraine

Kherson Regional Oncological Dispensary; 🇺🇦 Kherson, Ukraine

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States