Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Sirolimus

Mitogens

Erlotinib Hydrochloride

Temsirolimus

MTOR Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Tyrosine

Erlotinib hydrochloride (Tarceva) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. During the treatment period, patients will receive single-agent Tarceva, 150 mg/day.

Sirolimus (Rapamune) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.

Patients will receive single-agent Tarceva, 150 mg/day

Erlotinib hydrochloride

Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.

Thomas W Flaig, MD

The purpose of this study is to test the safety and efficacy of the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™) in the treatment of patients with metastatic kidney cancer.

Despite recent advances metastatic renal cell carcinoma remains an incurable condition. Currently available treatment with high-dose interleukin-2 can lead to complete responses in a small minority of selected patients but is markedly toxic and not broadly available. FDA-approved multikinase inhibitors (sorafenib and sunitinib malate) often cause partial and transient tumor regression. There is no standard treatment metastatic renal cell carcinoma for patients whose disease progressed on multikinase inhibitors. The kinase mammalian target of rapamycin (mTOR) is overstimulated in a subset of renal cell carcinomas and other malignancies and can be blocked by sirolimus leading to growth arrest. Erlotinib hydrochloride is a drug that blocks the function of the epidermal growth factor receptor (EGFR), often over expressed in kidney cancer. Sirolimus and EGFR inhibitors and been safely used in combination. In vitro experiments show that erlotinib enhances the sirolimus induced growth impairment in a panel of renal cell carcinoma cells. In the present study patients with metastatic renal cell carcinoma whose disease progressed on multikinase inhibitors will be treated with the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™). This is a single arm trial with no placebo or drug-based control arm

Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma

A Phase II Single Arm Clinical Trial to Evaluate the Efficacy and Safety of the Combination of Tarceva™ (Erlotinib Hydrochloride) and Rapamune™ (Sirolimus) in the Treatment of Metastatic Renal Cell Carcinoma.

Time to progression was defined as the time from beginning of therapy until disease progression or death. For subjects who had not progressed at the time of statistical analysis, progression-free survival was censored at the date of their last tumor assessment. Kaplan-Meier method was used to estimate median progression-free survival. Progression was defined as radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (year 2000 version), non-compliance in obtaining scans, unequivocal clinical progression or the initiation of another medication for the treatment of renal cell carcinoma.

For all subjects who had not died at the time of statistical analysis, duration of survival will was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the magnitude of the treatment effect as described for progression-free survival.

Genentech, Inc.

University of Colorado, Denver

Monitoring included patient interview, physical exam, routine laboratory tests (even in absence of symptoms) and appropriate work-up of any new symptoms or laboratorial abnormalities.

Erlotinib (Tarceva) therapy was started at 150 mg by mouth daily from day 1 to be taken at least 1 hour before or 2 hours after a meal. Sirolimus was initiated on day 8 (D8) with a loading dose of 6mg by mouth, followed by a daily dose of 2mg by mouth, on the basis of the product prescribing information for low-to-moderate immunologic risk renal transplant patients.

Erlotinib and Sirolimus

Age, Continuous

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Ethnicity (NIH/OMB)

United States

Region of Enrollment

It was calculated that 25 participants will provide 80% power to detect an improvement in progression-free survival from 12 to 24 weeks in a pretreated population of renal cell carcinoma patients.

One limitation of this study was the lack of von Hippel-Lindau (VHL) mutational status assessment.

Dr. Thomas Flaig

Per protocol analysis was used and 25 participants that were enrolled in the study were included in the analysis.

Progression-free Survival

Overall Survival

Overall Study

Gland and Hormone Related Diseases

Carcinoma, Endometrioid

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Ovarian Neoplasms

Ovarian Diseases

Adnexal Diseases

Gonadal Disorders

Endocrine System Diseases

Ovarian Cancer

25 mg administered intravenously, infused over a 30- to 60-minute period once weekly for 28 days (Total doses: 4 doses).

Andrés Poveda, Oncologist

Type of Application: Clinical trial of new indication.

Experimental drug: The study dose of temsirolimus will be 25 mg administered intravenously, infused over a 30- to 60-minute period once weekly for 28 days (Total doses: 4 doses). Temsirolimus is a selective inhibitor of mTOR (mammalian target of rapamycin). Pharmacotherapeutic group: Protein Kinase Inhibitors; ATC code: L01X E09.

Primary Objective:

* To identify in tumor samples future biomarkers associated with a short term exposure to temsirolimus.
* This is an exploratory clinical study. No efficacy objectives are included in this clinical trial.

Secondary Objectives:

* To estimate the tolerability for all temsirolimus-treated patients throughout the study and up to 28 days after the last dose of temsirolimus.
* To correlate observed changes with the different type of endometrial carcinoma (type I and type II), with regard to proteins related to mTOR (p4EBP1, pS6K1, c-MYC, cyclin D, p27, BAD, p53, Bcl-2 PTEN, pAKT, mTOR),
* To estimate the potential predictive value of some biomarkers (immunostaining for PTEN, pAKT, mTOR), relevant mutations in PTEN, PI3KCA, k-RAS, CTNNB1, and microsatellite instability status.
* To estimate the prognostic value of Ki67 expression after short-term presurgical therapy exposure
* To collect data about the differences in expression profile, assessed by RNA microarrays

POEM STUDY: A Phase IIa Trial in Endometrial Carcinoma With Temsirolimus

"A Phase IIa Pharmacokinetic-pharmacodynamic Study to Confirm the Inhibitory Effect of Temsirolimus, Targeting the mTOR Pathway in Endometrial Carcinoma"

To evaluate the mTOR inhibitor effects, assessed by level 4EBP1 and S6K1, of temsirolimus directly on endometrial tumor tissue after four weeks of therapy.

To evaluate if mTOR inhibition is associated with changes in tumor-tissue:

* Signal transduction: AKT and PTEN
* c-MYC, cyclin D activity
* Proliferation index analysis: p53, p27, BAD, Bcl-2 and ki-67

MedSIR

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

Neoplastic Processes

Bone Density Conservation Agents

Tamoxifen

Everolimus

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

20mg daily (1 cap) until unbearable toxicity or progression

10mg daily (2 caps of 5mg) until unbearable toxicity or progression

Tamoxifen is a classical treatment for breast metastatic cancer after 3rd generation anti-aromatase hormonotherapy in adjuvant or in metastatic line. The Tamoxifen efficacy is lowered by the hormonoresistance mechanisms due to the primary use of the anti-aromatases. The Pi3K-AKT-mTor pathway is frequently associated to the hormonoresistance mechanisms. This study is aimed to check if the inhibition of this signal transduction pathway by a synthetic mTor inhibitor (Everolimus) could improve the efficacy of the Tamoxifen.

Tamoxifen-RAD001 Versus Tamoxifen Alone in Patients With Anti-aromatase Resistant Breast Metastatic Cancer

Phase 2 Study Assessing the Tolerance and Efficacy of Tamoxifen Alone Versus the Association Tamoxifen-RAD001 (Everolimus) in Patients With Anti-aromatase Resistant Breast Metastatic Cancer

Novartis

ARCAGY/ GINECO GROUP

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma	NCT00353301	Renal Cell Carc...	Erlotinib hydro... Sirolimus	18 Years -	University of Colorado, Denver
Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma	NCT00353301	Renal Cell Carc...	Erlotinib hydro... Sirolimus	18 Years -	University of Colorado, Denver
POEM STUDY: A Phase IIa Trial in Endometrial Carcinoma With Temsirolimus	NCT02093598	Carcinoma, Endo... mTOR Protein	Temsirolimus	18 Years -	MedSIR
Tamoxifen-RAD001 Versus Tamoxifen Alone in Patients With Anti-aromatase Resistant Breast Metastatic Cancer	NCT01298713	Breast Neoplasm... mTor Protein	Tamoxifen Everolimus	18 Years -	ARCAGY/ GINECO GROUP
Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma	NCT00353301	Renal Cell Carc...	Erlotinib hydro... Sirolimus	18 Years -	University of Colorado, Denver

Spots Global Cancer Trial Database for mtor protein

Every month we try and update this database with for mtor protein cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.