Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium

NCT00805129 | Completed Phase 2 Results DMC

• 1 other identifier: 08-123
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn what effects, good and/or bad, Everolimus has on advanced urothelial cancer. The goal of this clinical research study is to learn if the study drug Everolimus can shrink or slow the growth of urothelial cancer. The safety of this drug will also be studied. The patients physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Everolimus is safe and effective.

Conditions

Bladder Cancer; Metastatic Transitional Cell Carcinoma

Keywords

URETER; URINARY BLADDER; RAD001; Everolimus; Urothelium; 08-123

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Were Progression Free at 2 Months

  To measure the two-month PFS rate of Everolimus (RAD001) as determined by RECIST. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  2 months

• Number of Participants Evaluated for Toxicity

  To determine the safety and toxicity of Everolimus (RAD001) in this patient population with toxicities being evaluated by CTCAE v3.0

  through study completion, up to 25 months

Secondary Outcomes (2)

• Response Rate

  through study completion, up to 25 months

• Proportion of Pretreatment Primary Tumor Samples With mTOR Pathway Markers

  25 months

Study Arms (1)

Everolimus

EXPERIMENTAL

Everolimus will be administered at a dose of 10 mg orally once daily continuously.

Drug: Everolimus

Interventions

Everolimus DRUG

Everolimus (RAD001) is a novel oral derivative of rapamycin. Everolimus will be administered orally as a once-daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take Everolimus in the morning, at the same time each day. Everolimus should be taken by the patient in a fasting state or with no more than a light fat-free meal.

Everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis, with histological confirmation at MSKCC.
• Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging.
• Patients must have at least one measurable site of disease (according to RECIST criteria) that has not been previously irradiated.
• Patients must have been previously treated, as defined by the following:
• Treatment with at least one prior cytotoxic agent but not more than four prior cytotoxic agents. Up to four prior chemotherapy agents are allowed, since conventional chemotherapy ranges from just one drug (e.g., gemcitabine) to regimens that contain four agents (e.g., M-VAC is a four-drug regimen containing methotrexate, vinblastine, doxorubicin, and cisplatin).
• The prior therapy must have included at least one of the following: cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine.
• The prior cytotoxic agents may have been administered in the perioperative or metastatic setting and may have been administered sequentially (e.g., first-line treatment followed by second-line treatment at time of progression) or as part of a single regimen.
• Patients must have pre-treatment tumor tissue available for analysis of m-TOR pathway markers. One paraffin block or 10 freshly-prepared unstained slides (on positively charged slides for immunohistochemistry) from the most representative single paraffin-embedded tumor tissue block. Slides from the primary tumor are preferred. If both the primary and metastatic tumor blocks are available, 10 slides from each of the sites should be submitted. If tissue from the primary tumor is not available, a paraffin block or unstained slides from a metastatic site are acceptable. Fine needle aspirates (FNAs) have insufficient tumor tissue and are not permitted.
• Age ≥ 18 years
• Karnofsky Performance Status ≥ 60%
• Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb \>9 g/dL
• Adequate liver function as shown by:
• serum bilirubin ≤ 1.5 x ULN
• INR \< 1.3 (or \< 3 on anticoagulants)
• ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients who may require major surgery during the course of the study.
• Prior treatment with any investigational drug within the preceding 4 weeks.
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. Patients receiving these corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with Everolimus. Topical or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
• Evidence of another active cancer, except for non-melanoma skin carcinoma, in-situ carcinoma of the cervix curatively treated, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York Heart Association Class III or IV.
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease.
• Severely impaired lung function as evidenced by:
• (TLC) \<50% predicted, OR (FVC) \<50% predicted OR, (DLCO) \<40% predicted
• Uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN.
• Active (acute or chronic) or uncontrolled severe infections.
• Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (2)

• Milowsky MI, Iyer G, Regazzi AM, Al-Ahmadie H, Gerst SR, Ostrovnaya I, Gellert LL, Kaplan R, Garcia-Grossman IR, Pendse D, Balar AV, Flaherty AM, Trout A, Solit DB, Bajorin DF. Phase II study of everolimus in metastatic urothelial cancer. BJU Int. 2013 Aug;112(4):462-70. doi: 10.1111/j.1464-410X.2012.11720.x. Epub 2013 Apr 3.

  PMID: 23551593 DERIVED

• Iyer G, Hanrahan AJ, Milowsky MI, Al-Ahmadie H, Scott SN, Janakiraman M, Pirun M, Sander C, Socci ND, Ostrovnaya I, Viale A, Heguy A, Peng L, Chan TA, Bochner B, Bajorin DF, Berger MF, Taylor BS, Solit DB. Genome sequencing identifies a basis for everolimus sensitivity. Science. 2012 Oct 12;338(6104):221. doi: 10.1126/science.1226344. Epub 2012 Aug 23.

  PMID: 22923433 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Dean Bajorin, MD
• Organization: Memorial Sloan Kettering Cancer Center

bajorind@mskcc.org

646-888-4700

Study Officials

• Dean Bajorin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2008
• First Posted: December 9, 2008
• Study Start: December 5, 2008
• Primary Completion: December 15, 2021
• Study Completion: December 15, 2021
• Last Updated: November 25, 2022
• Results First Posted: November 25, 2022

Record last verified: 2021-12

Locations

US (1)