Gemcitabine and Split-Dose Cisplatin Plus Everolimus (RAD001) in Patients With Advanced Solid Tumor Malignancies

NCT01182168 | Completed Phase 1

• 1 other identifier: 10-106
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety of gemcitabine and cisplatin plus Everolimus (also called RAD001) at different dose levels. We want to find out what effects, good and/or bad, this treatment has on you and your cancer. Gemcitabine and cisplatin are standard chemotherapy drugs that are commonly used to treat advanced urothelial cancer. Everolimus is a pill that works by shutting down some of the pathways in cancer cells that make tumors grow. Laboratory studies have shown that Everolimus appears to improve the activity of cisplatin against cancer cells.

Conditions

Bladder Cancer; Renal Pelvis Cancer; Ureter Cancer

Keywords

CISPLATIN; GEMCITABINE; RAD001 (EVEROLIMUS); 10-106

Outcome Measures

Primary Outcomes (1)

• To establish the dose-limiting toxicity (DLT)

  of Everolimus in combination with gemcitabine and split-dose cisplatin in patients with advanced urothelial cancer.

  2 years

Secondary Outcomes (8)

• To establish the maximum tolerated dose (MTD)

  2 years

• To evaluate the response rate

  2 years

• To evaluate the time to disease progression

  2 years

• To assess activated mTOR pathway markers

  2 years

• To evaluate overall survival

  2 years

Study Arms (1)

gemcitabine and cisplatin plus Everolimus

EXPERIMENTAL

This is a single-institution phase I study of gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001) in patients with advanced urothelial cancer.

Drug: gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001)

Interventions

gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001) DRUG

Patients will receive gemcitabine IV and cisplatin IV on days 1 and 8. Everolimus orally will be administered continuously (one cycle = 21 days). Everolimus will be escalated at the following dose levels: 5mg every-other-day, 5mg daily, and 10mg daily. Patients will receive a total of 6 cycles of gemcitabine and cisplatin in combination with Everolimus unless disease progression or unacceptable toxicity occurs.

gemcitabine and cisplatin plus 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 advanced urothelial cancer histologically confirmed by MSKCC pathology review.
• Patients may not have received prior systemic chemotherapy for metastatic disease.
• Patients may have received prior neoadjuvant or adjuvant systemic chemotherapy provided it was completed ≥ 1 year prior to the diagnosis of metastatic disease.
• Age ≥ 18 years.
• Karnofsky Performance Status ≥ 70.
• Expected survival of at least 3 months.
• Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedure to NCI CTCAE grade ≤ 1.
• Adequate bone marrow function as shown by:
• ANC ≥ 1.5x 109/L
• Platelets ≥ 100 x 109/L
• Hb \>9 g/dL
• Adequate liver function as shown by:
• Serum bilirubin ≤ 1.5 x ULN
• INR ≤ 1.5 (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, tyrosine kinase inhibitors, 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.

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 Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Ureteral Neoplasms

Interventions

Gemcitabine; 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; Ureteral Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Dean Bajorin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2010
• First Posted: August 16, 2010
• Study Start: August 1, 2010
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: March 31, 2016

Record last verified: 2016-03

Locations

US (1)