Clinical trial NCT02064725: Virexxa (Sodium Cridanimod) w/Progestin Therapy in Pts w/Progesterone Receptor Neg Recurrent/Persistent Endometrial CA
Official title: A Phase II Study of Sodium Cridanimod in Conjunction With Progestin Therapy in Patients With Progesterone Receptor Negative Recurrent or Persistent Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Recurrent or Persistent Endometrial Carcinoma
Keywords: Endometrial cancer
Recurrent or persistent endometrial carcinoma
Progesterone Receptor Negative
Sodium cridanimod
Virexxa
Lead sponsor: Kevelt AS
Sponsor class: INDUSTRY
Collaborators: name: Pharmasyntez
First posted: 2014-02-17
Enrollment: 8
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: 12 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: 24 months
measure: Time to response
timeFrame: 12 months
measure: Time to progression
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
measure: Overall Disease Control Rate
timeFrame: 24 months
Other outcomes:
measure: Progesterone receptor (PrR) levels
timeFrame: 1 months
Locations:
city: San Jose
country: United States
facility: Physicians Research Group
state: California
city: Santa Rosa
country: United States
facility: St. Jude Hospital Yorba Linda, St. Joseph's Heritage Healthcare
state: California
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brest
country: Belarus
facility: Brest Regional Clinical Hospital
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncology Dispensary
city: Minsk
country: Belarus
facility: N.N. Alexandrov National Cancer Centre of Belarus
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Oncology Dispensary
city: Brno
country: Czech Republic
facility: Masaryk Memorial Cancer Institute
city: Hradec Kralove
country: Czech Republic
facility: University Hospital Hradec Kralove
city: Olomouc
country: Czech Republic
facility: University Hospital Olomouc, Oncology
city: Bratislava
country: Slovakia
facility: Oncology Institute of Saint Alzbeta
city: Poprad
country: Slovakia
facility: Poko Poprad, s.r.o.
city: Trencin
country: Slovakia
facility: University Hospital Trencin
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Oncology Dispensary
city: Dnipropetrovsk
country: Ukraine
facility: Municipal Institution of Dnipropetrovsk Regional Rada
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Oncology Center
city: Kharkiv
country: Ukraine
facility: S.P. Grigoryeva Institute of Medical Radiology
city: Kherson
country: Ukraine
facility: Kherson Regional Oncological Dispensary
city: Sumy
country: Ukraine
facility: Sumy State University
city: Vinnitsa
country: Ukraine
facility: Vinnitsa Regional Clinical Oncology Center
Study officials:
affiliation: Kevelt AS
name: Laura L. Douglass
role: STUDY_DIRECTOR
References: