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Efficacy,Tolerability,Safety of Temsirolimus in Women With Platinum-refractory Ovarian Carcinoma or Advanced Endometrial Carcinoma

Phase 2
Completed
Conditions
Ovarian Neoplasms
Endometrial Neoplasms
Genital Diseases, Female
Ovarian Diseases
Interventions
Registration Number
NCT01460979
Lead Sponsor
AGO Study Group
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
47
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TemsirolimusTemsirolimus-
Primary Outcome Measures
NameTimeMethod
progression-free survivalafter 4 months for ovarian cancer and 6 months for endometrial carcinoma after study entry
Secondary Outcome Measures
NameTimeMethod
safety and toxicity, i.e. type, frequency, severity and duration of adverse reactionsweekly until progression; thereafter every 8 weeks
quality of life according to European Organisation for Research and Treatment of Cancer (EORTC) questionaires "QLQ C30", "QLQ OV28" and "QLQ-EN24"every 8 weeks
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 cancerevery 8 weeks until progression
progression-free survival according to RECIST 1.1 and cancer antigen 125 (CA 125) (for ovarian cancer) (biological progression-free survival (PFSbio))every 8 weeks until progression
overall survivalweekly until progression; thereafter every 8 weeks
rate and duration of stable diseases according to RECIST-criteria for endometrial cancerevery 8 weeks until progression

Trial Locations

Locations (18)

Universitätsklinikum Schleswig-Holstein, Campus Kiel

🇩🇪

Kiel, Schleswig-Holstein, Germany

Universitätsklinikum Ulm

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Ulm, Baden-Württemberg, Germany

Universitätsklinikum Gießen-Marburg, Standort Marburg

🇩🇪

Marburg, Hessen, Germany

Klinikum rechts der Isar der Technischen Universität

🇩🇪

München, Bayern, Germany

Universität Erlangen-Nürnberg

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Erlangen, Bayern, Germany

Klinikum der J. W. Goethe-Universität

🇩🇪

Frankfurt am Main, Hessen, Germany

Gynäkologisch-onkologische Praxis

🇩🇪

Hannover, Niedersachsen, Germany

Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität

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Greifswald, Mecklenburg Vorpommern, Germany

Klinikum Göttingen, Georg-August-Universität

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Göttingen, Niedersachsen, Germany

Klinikum Offenbach

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Offenbach, Hessen, Germany

Universitätsklinikum Essen

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Essen, Nordrhein-Westfalen, Germany

Kliniken Essen Mitte, Evang. Huyssens Stiftung/Knappschaft GmbH

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Essen, Nordrhein-Westfalen, Germany

Medizinische Hochschule Hannover

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Hannover, Niedersachsen, Germany

Städt. Klinikum Solingen gGmbH

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Solingen, Nordrhein-Westfalen, Germany

Charité, Campus Virchow Klinikum

🇩🇪

Berlin, Germany

Universitätsklinikum Carl Gustav Carus

🇩🇪

Dresden, Sachsen, Germany

Universitätsklinikum Hamburg-Eppendorf

🇩🇪

Hamburg, Germany

GYNAEKOLOGICUM Bremen

🇩🇪

Bremen, Germany

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