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

Sponsor

AGO Study Group (Other)

Overall Status

Completed

CT.gov ID

NCT01460979

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Genital Diseases, Female Ovarian Diseases Ovarian Neoplasms Endometrial Neoplasms	Drug: Temsirolimus	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Temsirolimus	Drug: Temsirolimus 25mg weekly intravenous until progression

Arm

Intervention/Treatment

Experimental: Temsirolimus

Drug: Temsirolimus

25mg weekly intravenous until progression

Outcome Measures

Primary Outcome Measures

progression-free survival [after 4 months for ovarian cancer and 6 months for endometrial carcinoma after study entry]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitätsklinikum Ulm	Ulm	Baden-Württemberg	Germany	89075
2	Universität Erlangen-Nürnberg	Erlangen	Bayern	Germany	91054
3	Klinikum rechts der Isar der Technischen Universität	München	Bayern	Germany	81675
4	Klinikum der J. W. Goethe-Universität	Frankfurt am Main	Hessen	Germany	60590
5	Universitätsklinikum Gießen-Marburg, Standort Marburg	Marburg	Hessen	Germany	35043
6	Klinikum Offenbach	Offenbach	Hessen	Germany	63069
7	Universitätsklinikum Greifswald der Ernst-Moritz-Arndt-Universität	Greifswald	Mecklenburg Vorpommern	Germany	17475
8	Klinikum Göttingen, Georg-August-Universität	Göttingen	Niedersachsen	Germany	37075
9	Gynäkologisch-onkologische Praxis	Hannover	Niedersachsen	Germany	30177
10	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
11	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen	Germany	45122
12	Kliniken Essen Mitte, Evang. Huyssens Stiftung/Knappschaft GmbH	Essen	Nordrhein-Westfalen	Germany	45136
13	Städt. Klinikum Solingen gGmbH	Solingen	Nordrhein-Westfalen	Germany	42653
14	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen	Germany	01307
15	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel	Schleswig-Holstein	Germany	24105
16	Charité, Campus Virchow Klinikum	Berlin		Germany	13353
17	GYNAEKOLOGICUM Bremen	Bremen		Germany	28211
18	Universitätsklinikum Hamburg-Eppendorf	Hamburg		Germany	20251