Sorafenib Tosylate and Everolimus in Treating Patients With Advanced Solid Tumors and Metastatic Pancreatic Cancer That Does Not Respond to Gemcitabine Hydrochloride

NCT00981162 | Completed Phase 1 DMC

• 2 other identifiers: I 150109NCI-2009-01326
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial is studying the side effects and best dose of everolimus when given together with sorafenib tosylate and to see how well they work in treating patients with advanced solid tumors and metastatic pancreatic cancer that does not respond to gemcitabine hydrochloride. Sorafenib tosylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Giving sorafenib tosylate together with everolimus may kill more tumor cells.

Conditions

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Overall survival (Phase II)

  The estimated distribution of overall survival will be obtained using the product-limit based Kaplan-Meier method. Estimates of quantities such as median survival will be obtained.

  Time from date of subject enrollment to the date of death due to any cause, assessed up to 6 months

• Maximum tolerated dose of everolimus (Phase I)

  Assessed by National Cancer Institute (NCI) CTCAE v3.0.

  28 days

Secondary Outcomes (5)

• Overall response rate (Phase II)

  Up to 1 year

• Differences in biomarkers between responders and non-responders (Phase II)

  Baseline and days 1 and 15 of course 1

• PK parameters (Phase II)

  Baseline and days 1 and 15 of course 1

• Correlation of predicted drug concentration or area under the curve (AUC) with biomarker response for each drug and/or in combination (Phase II)

  Baseline and days 1 and 15 of course 1

• Toxicity and adverse events as assessed by NCI CTCAE v3.0

  Up to 30 days post-treatment

Study Arms (1)

Treatment (sorafenib tosylate and everolimus)

EXPERIMENTAL

Patients receive everolimus PO once daily and sorafenib tosylate PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: sorafenib tosylate; Drug: everolimus; Other: laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

Interventions

sorafenib tosylate DRUG

Given PO

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

Treatment (sorafenib tosylate and everolimus)

everolimus DRUG

Given PO

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Treatment (sorafenib tosylate and everolimus)

laboratory biomarker analysis OTHER

Correlative study

Treatment (sorafenib tosylate and everolimus)

pharmacogenomic studies OTHER

Correlative study

Also known as: Pharmacogenomic Study

Treatment (sorafenib tosylate and everolimus)

pharmacological study OTHER

Correlative study

Also known as: pharmacological studies

Treatment (sorafenib tosylate and everolimus)

Eligibility Criteria

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

You may qualify if:

• Phase I only: Histologically or cytologically confirmed solid tumors that are advanced and refractory to or lack life-prolonging treatments; patients with histologically or cytologically confirmed renal cell carcinoma and hepatocellular carcinoma will be eligible
• Phase II: Histologically or cytologically proven metastatic adenocarcinoma of pancreas that had progressed after one prior gemcitabine containing regimen, or progressed within 6 months of the completion of gemcitabine containing adjuvant regimen
• Patients must have measurable or assessable disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate hematological, renal and liver functions as determined by the following:
• Absolute neutrophil count (ANC) \> 1500 cells/mm\^3
• Hemoglobin \>= 9g/dL
• Platelets \>= 100,000 cells/mm\^3
• Serum creatinine within institutional upper limit of normal (ULN) OR \>= 60mll/min for patients with creatinine levels above institutional ULN
• Bilirubin =\< 1.5 x ULN
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 times ULN (\< 5 x ULN for patients with abnormal values attributable to liver metastases)
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 times ULN (\< 5 x ULN for patients with abnormal values attributable to liver metastases)
• International normalized ratio (INR) =\< 1.5 (Anticoagulation is allowed if target INR =\< 1.5 on a stable dose of warfarin or on a stable dose of low-molecular-weight (LMW) heparin for \> 2 weeks at the first dose of study agent)
• Fasting serum cholesterol =\< 300 mg/dL OR =\< 7.75 mmol/L AND Fasting triglycerides =\<2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
• Ability to understand and willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures

You may not qualify if:

• Phase II: Patients in whom histological or cryological diagnosis is not consistent with adenocarcinoma including adenosquamous, islet cell, cystoadenoma or cystadenocarcinoma, carcinoid, small or large cell carcinoma or lymphoma
• Phase II: Adenocarcinoma arising from a site other than the pancreas (distal bile duct, ampulla of vater or periampullary duodenum)
• Prior therapy with approved or investigational agents within 4 weeks prior to the start of treatment plan in this protocol
• Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 x ULN
• Any active infections
• Cardiac disease: Congestive heart failure \> class II New York Heart Association (NYHA); patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management
• Cerebrovascular accident including transient ischemic attacks within the past 6 months
• Pulmonary hemorrhage/bleeding event \>= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug
• Any other hemorrhage/bleeding event \>= CTCAE Grade 3 within 4 weeks of first dose of study drug
• Serious non-healing wound, ulcer, or bone fracture
• Known or suspected allergy to sorafenib, everolimus, other rapamycins (sirolimus, temsirolimus), their excipients, or any agent given in the course of this trial
• Any condition that impairs patient's ability to swallow whole pills
• Any malabsorption problem

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Bayer: collaborator

Study Sites (2)

University of Colorado at Denver Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Sorafenib; Everolimus; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Sirolimus; Macrolides; Lactones; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Wen Wee Ma

  Roswell Park Cancer Institute

  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: September 21, 2009
• First Posted: September 22, 2009
• Study Start: August 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: December 1, 2012
• Last Updated: September 13, 2022

Record last verified: 2022-09

Locations

US (2)