Cisplatin and Everolimus in Treating Patients With Advanced Solid Tumors

NCT00423865 | Completed Phase 1

• 2 other identifiers: MSKCC 06-129MSKCC-06129
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Everolimus may also help cisplatin work better by making tumor cells more sensitive to the drug. Giving cisplatin together with everolimus may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with cisplatin in treating patients with advanced solid tumors or recurrent or metastatic solid tumors.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific; CISPLATIN; RAD001 (EVEROLIMUS); 06-129

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose of everolimus

  1 year

Secondary Outcomes (2)

• Pharmacokinetic profile of cisplatin and everolimus

  1 year

• Pharmacodynamic profile of cisplatin and everolimus

  1 year

Study Arms (1)

cisplatin & RAD001

EXPERIMENTAL

This will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors

Drug: cisplatin; Drug: everolimus; Genetic: gene expression analysis; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: biopsy

Interventions

cisplatin DRUG

cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15)

cisplatin & RAD001

everolimus DRUG

escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle)

cisplatin & RAD001

gene expression analysis GENETIC

Each biopsy specimen will be formalin-fixed and paraffin-embedded for IHC, and analysis of p53 and p21 will follow methods previous reported by our group. The avidin-biotin immunoperoxidase technique will be employed.

cisplatin & RAD001

immunohistochemistry staining method OTHER

After the phase 2 recommended dose is established in the phase I portion of the study (Part A), we plan to enroll an additional 6 patients for pharmacodynamic studies (Part B). Entry into Part B requires the patient have tumor tissue which is easily accessible for research biopsy. The patients will be asked to provide written informed consent for the research biopsies. Patients also will be asked to provide written informed consent to allow the use of their tissue for future research studies. The research biopsies are not mandatory for any patient. Patients who do not consent to the research biopsies or who withdraw consent for the research biopsies may still receive RAD001 + cisplatin in the study

cisplatin & RAD001

laboratory biomarker analysis OTHER

Laboratory data (complete blood count, comprehensive metabolic panel including magnesium) regarding adverse events will be collected on each cisplatin treatment day. Additional adverse event data will be collected at regularly scheduled clinic visits at which history and physical are performed by the investigator (Cycle 1 - Days 1, 8, 15, and 21. Cycle 2 - Days 1 and 15. Cycle 3 and beyond - Day 1)

cisplatin & RAD001

pharmacological study OTHER

For patients in Part A, research bloods for pharmacokinetics are drawn on Day 1 and Day 8.

cisplatin & RAD001

biopsy PROCEDURE

"Pre-treatment Research Biopsy:" Within 14 days prior to treatment, research biopsy (of primary tumor, metastatic deposit, or involved lymph node) will be performed. Baseline labs should be drawn within 14 days of the research biopsy. The biopsy sample will be formalin-fixed and paraffin-embedded for immunohistochemistry. Post-treatment Research Biopsy:" Research biopsy (of primary tumor, metastatic deposit, or involved lymph node) will be requested again for Day 15 of Cycle 1, prior to administration of RAD001 and cisplatin on that day.

cisplatin & RAD001

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following: * Advanced solid tumor (part A) * Confirmation by core biopsy or fine-needle aspiration allowed * Solid tumor (part B) * Recurrent or metastatic disease * Easily accessible for biopsy * Measurable disease * No uncontrolled brain or leptomeningeal metastases * No requirement for glucocorticoids PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin \> 10 g/dL * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN (\< 5 times ULN if liver metastases are present) * Creatinine normal OR creatinine clearance ≥ 55 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy * No HIV positivity * No peripheral neuropathy ≥ grade 2 * No hypertriglyceridemia ≥ grade 2 * No impaired gastrointestinal function or gastrointestinal disease that may alter the absorption of everolimus, including any of the following: * Ulcerative disease * Uncontrolled nausea * Vomiting * Diarrhea * Malabsorption syndrome * Small bowel resection * No other concurrent severe and/or uncontrolled medical disease that would compromise study participation, including any of the following: * Uncontrolled diabetes * Unstable angina * New York Heart Association class III or IV congestive heart failure PRIOR CONCURRENT THERAPY: * No more than 3 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease * At least 4 weeks since prior major surgery and recovered * At least 4 weeks since prior radiation therapy and recovered * At least 4 weeks since prior systemic anticancer therapy and recovered * At least 4 weeks since prior and no other concurrent investigational drugs * No prior everolimus or other agents specifically targeting mTOR * No prior radiation therapy to \> 25% of the bone marrow * No prior radiation therapy to the whole pelvis and/or brain * No concurrent chronic steroid treatment (\> 5 mg/day of prednisone) * Concurrent low-dose steroid replacement regimens (≤ 5 mg/day of prednisone) allowed * No concurrent immunosuppressive agents * No other concurrent anticancer agents * No concurrent agents known to be strong inhibitors or inducers of isoenzyme CYP3A

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Interventions

Cisplatin; Everolimus; Gene Expression Profiling; Immunohistochemistry; Biopsy

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Sirolimus; Macrolides; Lactones; Organic Chemicals; Genetic Techniques; Investigative Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Matthew G. Fury, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• David G. Pfister, 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: January 16, 2007
• First Posted: January 18, 2007
• Study Start: November 1, 2006
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: May 25, 2015

Record last verified: 2012-09

Locations

US (1)