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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Genital Diseases, Female, Ovarian Diseases, Ovarian Neoplasms, Endometrial Neoplasms

Intervention / Treatment
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* Drug: Temsirolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temsirolimus<br> | Drug: Temsirolimus<br>* 25mg weekly intravenous until progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | after 4 months for ovarian cancer and 6 months for endometrial carcinoma after study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | every 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 survival |  | weekly until progression; thereafter every 8 weeks | 
| safety and toxicity, i.e. type, frequency, severity and duration of adverse reactions |  | weekly 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 RECIST-criteria for endometrial cancer |  | every 8 weeks until progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Cancer, Endometrial Carcinoma, Temsirolimus