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

AGO Study Group

Status and phase

Completed

Phase 2

Conditions

Ovarian Neoplasms

Genital Diseases, Female

Endometrial Neoplasms

Ovarian Diseases

Treatments

Drug: Temsirolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT01460979

AGO-GYN 8

Details and patient eligibility

About

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.

Enrollment

47 patients

Sex

Female

Ages

18+ years old

Volunteers

No 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