Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

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

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

This is a single-arm study. All patients will receive everolimus.

David F McDermott, MD

The purpose of this study is to determine if certain features of tumor specimens sampled prior to therapy can predict for the likelihood of responding to everolimus.

* Participants will undergo a CT or ultrasound guided biopsy of an accessible tumor lesion before beginning the study medication.
* Everolimus tablets will be taken orally once a day. Participants will undergo a physical exam and will be asked questions about their general health and specific questions about any problems they might be having. Photographs will be taken of the tumor to assess the response to treatment. This will be done by a CT or MRI scan. Blood tests will be performed every 4 weeks. In addition, blood for research purposes will be done on day 1 of every other cycle. A urine test will be done every 4 weeks.

Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma

A Phase II Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma

The biomarkers of interest are pS6 and pAkt. Expression will be classified as low, intermediate, or high based on a composite score of staining intensity and % of tumor cells staining positive. The difference in progression free survival (PFS) time in the "low" to "high" groups is analyzed. PFS is the time from start of treatment to disease progression (PD) or death (estimated by Kaplan Meier method)s. Patients without PD and alive are censored at last date patient is known PD-free. PD is defined by Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST) as follows:

* \>20% increase in the sum of the diameters (SD) of target lesions, referencing the smallest SD on study (including baseline). Must be an increase of \>5 mm.
* New lesions or PD of non-target lesions. Must be represent overall disease status change, not a single lesion increase. Patients with PD at the first on-treatment imaging assessment, will remain on study at investigator discretion until later confirmed.

Progression free survival (PFS) is defined as the time from start of treatment to disease progression (PD) or death from any cause as estimated by Kaplan Meier methods. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free. Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST) as follows:

- \>20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including baseline if it's the smallest). The sum must also demonstrate an increase of \>5 mm.

OR

-Appearance of new lesions and/or unequivocal progression of non-target lesions. It must be representative of overall disease status change, not a single lesion increase. For patients with PD at the first on-treatment imaging assessment, patients will be allowed to remain on study until confirmation at the next assessment at investigator discretion if patient is benefiting from treatment.

The best overall response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria.

CR and PR must meet the following lesion criteria without having any new lesions as well:

Target Lesion:

(CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

(PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Non-Target Lesion:

(CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis).

Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.

Next generation sequencing was used to identify participants with PI3K-AKT-MTOR mutations. Best overall response rate was analyzed with mutant versus wild-type pathways. Please see Best Overall Response Rate for response definition.

Dana-Farber Cancer Institute

Duke University

Novartis

Beth Israel Deaconess Medical Center

Director of Biologic Therapy Program

This is a single-arm study. All patients will receive everolimus.

Everolimus: Tablet form taken orally once a day

Treatment

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

00- Fully Active

01- Restricted 02 - Ambulatory and Capable of Self Care

ECOG Performance Status

Prior Lines of Therapy

Clear Cell

Papillary

Missing

Histology

Favorable (0 risk factors)

Intermediate (1-2 risk factors)

High (>=3 risk factors)

Memorial Sloan Kettering Cancer Center Risk Class

High (≥3 risk factors)

International Metastatic Renal-Cell Carcinoma Database Consortium Class

Yes, Radical

Yes, Partial

Prior Nephrectomy

Bone

Liver

Lung

Brain

Renal

Pancreas

Lymph Nodes, Intra-Abdominal

Lymph Node, Pulmonary

Adrenal Glands

Other

Metastatic Sites

Rupal Bhatt

Phospho-Akt and phospho-S6 immunohistochemistry analysis was unsuccessful due to the lack of adequate tissue samples and was not pursued further.

Difference in Median Progression Free Survival Time Between Favorable and Unfavorable Biomarker Group

Twenty-five patients enrolled onto the study between April 2009 and November 2012. One patient became ineligible because of the inability to obtain a pretreatment biopsy sample. A total of 27 tissue samples were successfully obtained from 24 patients, with 3 sets of paired tissues obtained before treatment and while receiving treatment.

Spots Global Cancer Trial Database for Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma

Trial Identification

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Interventions

Study Description

Keywords

Eligibility

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