Clinical trial NCT01460979: Efficacy,Tolerability,Safety of Temsirolimus in Women With Platinum-refractory Ovarian Carcinoma or Advanced Endometrial Carcinoma
Official title: Activity, Tolerability, Safety of Temsirolimus in Women With Ovarian Cancer Who Progressed During Previous Platinum Chemotherapy or Within 6 Months After Therapy or Advanced Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Genital Diseases, Female
Ovarian Diseases
Ovarian Neoplasms
Endometrial Neoplasms
Keywords: Ovarian Cancer
Endometrial Carcinoma
Temsirolimus
Lead sponsor: AGO Study Group
Sponsor class: OTHER
First posted: 2011-10-27
Enrollment: 47
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: The purpose of this study is to determine the activity, tolerability and safety of Temsirolimus in women with ovarian cancer who progressed during the previous platinum chemotherapy alternatively within 6 months from completion of therapy or advanced endometrial carcinoma.


Eligibility criteria: Inclusion Criteria:

* Women ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
* Before performance of study specific actions or assessment the patient has to be informed, has signed the written consent and is willing to follow the requirements concerning treatment and follow-up.Comment: Procedures which are according to common clinical routine and having been performed before having given written informed consent may be used for the purpose of screening procedures or initial medical assessment as long as these procedures follow the protocol.
* Required: negative pregnancy test in fertile women

Stratum A - Ovarian Cancer:

* Histologically confirmed Ovarian Cancer
* Platin-refractory relapsed disease: progression within a platin-based chemotherapy or within 6 months after completion of a platin-based chemotherapy
* Prior treatment with a taxane-based scheme
* minimum of one measurable or non-measurable tumor lesion(according to RECIST 1.1 criteria)
* Not more than 2 previous chemotherapies or cytostatic therapies (i.e. monoclonal antibodies, cytokines, signal transduction inhibitors)

Stratum B - Endometrian Cancer:

* Histologically confirmed Endometrian Cancer
* Advanced (International Federation of Gynaecology and Obstetrics (FIGO) III or IV) or relapsed diseases not amenable to potentially curative treatment with local surgery and/or radiation therapy
* Prior endocrine therapy is allowed
* Prior adjuvant chemotherapy is allowed
* Minimum of one measurable or non-measurable tumor lesion(according to RECIST 1.1 criteria)

Exclusion Criteria:

* ECOG \> 2
* Prior therapy with mammalian target of rapamycin (mTOR) -Inhibitor
* Cytostatic therapy (i.e. monoclonal antibodies, cytokines, signal transduction inhibitors), cytotoxical chemotherapy or endocrine therapy or radiation at the same time
* Current or recent treatment with another study drug and/or participation in another clinical study within 28 days prior to first dose of study treatment
* Chemotherapy or cytostatic therapy (i.e. monoclonal antibodies, cytokines, signal transduction inhibitors) or radiation within 28 days prior to start of study treatment
* Known or supposed hypersensitivity compared to study medication
* Acute or chronical infection
* Second malignancy which influences the prognosis of the patient
* Inadequate renal function (Creatinin \> 1.5 x Upper Limit of Normal (ULN))
* Inadequate liver function (aspartate transaminase (AST), alanine transaminase (ALT), gamma-Glutamyl transpeptidase (GGT) \> 2.5 x ULN or \> 5.0 x ULN in the presence of liver metastasis; Bilirubin \> 1.5 x ULN)
* Platelets \< 100.000 /μl; Absolute Neutrophil Count (ANC) \< 1.500 /μl
* Cachectic patients with weight \< 45kg
* Patients who need parenteral nutrition
* Patients with ileus within the last 28 days
* One of the following diseases within 12 months prior to first study treatment: myocardial infarction, severe/unstable angina, bypass surgery of the coronar- or peripheral vessels, symptomatic heart insufficiency, cerebrovascular insult, transient ischemic attack (TIA), pulmonary embolism, deep venous thrombosis, other thromboembolic events
* Current treatment with Cytochrome P450 3A4 (CYP3A4) -Inhibitors (i.e. protease inhibitors, antimycotics, calcium channel blocker, macrolide antibiotics, Cimetidine) or -inductors (i.e. Carbamazepin, Phenobarbital, Phenytoin, Rifampicin, amber)
* Uncontrolled hypertension (\> 150/100 mmHg despite optimal medicinal treatment)
* Current cardiac arrhythmias (Common Terminology Criteria for Adverse Events of National Cancer Institute (NCI CTCAE) grade ≥ 2), atrial fibrillation, prolongation of QTc \> 470 msec
* Left ventricular ejection fraction (LVEF) ≤ 50% defined by echocardiogram
* NCI CTCAE grade 3 hemorrhage within 4 weeks prior to beginning of treatment
* Symptoms which indicate brain metastases, spinal cord compression or give new indications for brain- or leptomeningeal metastases
* Human immunodeficiency virus (HIV) positive or manifested Acquired Immune Deficiency Syndrome (AIDS-disease)
* Patients with other severe diseases who represent an inadequate risk for study participation

Applicable only for patients with no hysterectomy and/or bilateral adnexectomy prior to start of study.

* lactation
* potential fertile women without adequate contraception (potential fertile women must use one of the following adequate contraception: complete abstinence, intrauterine spiral or another method with a failure quote \< 1% per year)
* life expectancy \< 3 months
* neurological or psychiatric diseases or drugs or alcohol abuse which suppose no adequate comprehension and consequently no effective consent to study participation or no acceptable compliance during the study
* predictable problems with the compliance to appointments for examinations

Primary outcomes:
measure: progression-free survival
timeFrame: after 4 months for ovarian cancer and 6 months for endometrial carcinoma after study entry
Secondary outcomes:
measure: rate and duration of stable diseases according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and Gynecologic Cancer Intergroup (GCIG)-criteria for ovarian cancer
timeFrame: every 8 weeks until progression
measure: progression-free survival according to RECIST 1.1 and cancer antigen 125 (CA 125) (for ovarian cancer) (biological progression-free survival (PFSbio))
timeFrame: every 8 weeks until progression
measure: overall survival
timeFrame: weekly until progression; thereafter every 8 weeks
measure: safety and toxicity, i.e. type, frequency, severity and duration of adverse reactions
timeFrame: weekly until progression; thereafter every 8 weeks
measure: quality of life according to European Organisation for Research and Treatment of Cancer (EORTC) questionaires "QLQ C30", "QLQ OV28" and "QLQ-EN24"
timeFrame: every 8 weeks
measure: rate and duration of stable diseases according to RECIST-criteria for endometrial cancer
timeFrame: every 8 weeks until progression
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universität Erlangen-Nürnberg
state: Bayern
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität
state: Bayern
city: Frankfurt am Main
country: Germany
facility: Klinikum der J. W. Goethe-Universität
state: Hessen
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen-Marburg, Standort Marburg
state: Hessen
city: Offenbach
country: Germany
facility: Klinikum Offenbach
state: Hessen
city: Greifswald
country: Germany
facility: Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität
state: Mecklenburg Vorpommern
city: Göttingen
country: Germany
facility: Klinikum Göttingen, Georg-August-Universität
state: Niedersachsen
city: Hannover
country: Germany
facility: Gynäkologisch-onkologische Praxis
state: Niedersachsen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Kliniken Essen Mitte, Evang. Huyssens Stiftung/Knappschaft GmbH
state: Nordrhein-Westfalen
city: Solingen
country: Germany
facility: Städt. Klinikum Solingen gGmbH
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charité, Campus Virchow Klinikum
city: Bremen
country: Germany
facility: GYNAEKOLOGICUM Bremen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
Study officials:
affiliation: AGO Study Group (Study Group of the Arbeitsgemeinschaft Gynaekologische Onkologie)
name: Günter Emons, Professor
role: STUDY_CHAIR
References: