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

A Phase II Study of Sodium Cridanimod in Conjunction With Progestin Therapy in Patients With Progesterone Receptor Negative Recurrent or Persistent Endometrial Carcinoma

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.

Study Overview

• Status: Unknown
• Conditions: Recurrent or Persistent Endometrial Carcinoma
• Intervention / Treatment: Drug: Sodium cridanimod

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belarus
  • Brest, Belarus
    • Brest Regional Clinical Hospital
  • Minsk, Belarus
    • N.N. Alexandrov National Cancer Centre of Belarus
  • Minsk, Belarus
    • Minsk City Clinical Oncology Dispensary
  • Vitebsk, Belarus
    • Vitebsk Regional Clinical Oncology Dispensary
• Czech Republic
  • Brno, Czech Republic
    • Masaryk Memorial Cancer Institute
  • Hradec Kralove, Czech Republic
    • University Hospital Hradec Kralove
  • Olomouc, Czech Republic
    • University Hospital Olomouc, Oncology
• Slovakia
  • Bratislava, Slovakia
    • Oncology Institute of Saint Alzbeta
  • Poprad, Slovakia
    • POKO Poprad, s.r.o.
  • Trencin, Slovakia
    • University Hospital Trencin
• Ukraine
  • Cherkasy, Ukraine
    • Cherkasy Regional Oncology Dispensary
  • Dnipropetrovsk, Ukraine
    • Municipal Institution of Dnipropetrovsk Regional Rada
  • Kharkiv, Ukraine
    • Kharkiv Regional Clinical Oncology Center
  • Kharkiv, Ukraine
    • S.P. Grigoryeva Institute of Medical Radiology
  • Kherson, Ukraine
    • Kherson Regional Oncological Dispensary
  • Sumy, Ukraine
    • Sumy State University
  • Vinnitsa, Ukraine
    • Vinnitsa Regional Clinical Oncology Center
• United States
  • California
    • San Jose, California, United States, 95124
      • Physicians Research Group
    • Santa Rosa, California, United States, 95403
      • St. Jude Hospital Yorba Linda, St. Joseph's Heritage Healthcare
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Sodium cridanimod; Eligible patients will be enrolled into the study and administered sodium cridanimod (500 mg i.m./ twice a week) in combination with megestrol acetate (160 mg p.o./ day) or medroxyprogesterone acetate (200 mg p.o./ day).; Other Names: Virexxa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	24 months
Overall survival	24 months
Time to progression	24 months
Time to response	12 months
Overall Disease Control Rate	24 months

Other Outcome Measures

Outcome Measure	Time Frame
Progesterone receptor (PrR) levels	1 months

Collaborators and Investigators

• Sponsor: Kevelt AS
• Collaborators: Pharmasyntez
• Investigators: Study Director: Laura L. Douglass, Kevelt AS

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (ANTICIPATED): January 1, 2018
• Study Completion (ANTICIPATED): July 1, 2018

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (ESTIMATE): February 17, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Endometrial cancer; Progesterone Receptor Negative; Recurrent or persistent endometrial carcinoma; Sodium cridanimod; Virexxa
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Disease Attributes; Carcinoma; Recurrence; Endometrial Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Interferon Inducers; 10-carboxymethyl-9-acridanone
• Other Study ID Numbers: VX-EC-2-2013