Carboplatin, Paclitaxel, and Everolimus in Treating Patients With Previously Untreated Cancer of Unknown Primary
Carcinoma of Unknown Primary Origin
About this trial
This is an interventional treatment trial for Carcinoma of Unknown Primary Origin focused on measuring Newly Diagnosed Carcinoma of Unknown Primary Origin, Squamous Cell Carcinoma of Unknown Primary Origin, Undifferentiated Carcinoma of Unknown Primary, newly diagnosed carcinoma of unknown primary
Eligibility Criteria
Inclusion Criteria
- Histological confirmation of metastatic adenocarcinoma, poorly differentiated non-small cell carcinoma, or poorly differentiated squamous carcinoma
- Adequate FFPE tissue or re-biopsy planned after registration but prior to treatment
- Measurable disease as defined; for patients having only lesions measuring at least 1 cm to =< 2 cm must use spiral computed tomography (CT) imaging for both pre- and post-treatment tumor assessments; disease that has received prior radiation (performed for palliative reasons) cannot be used for measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Hemoglobin (Hgb) >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1,500/uL
- Platelet count >= 100,000/uL
- Total bilirubin =< upper limits of normal (ULN); if liver metastases are present, total bilirubin =< 2 x ULN
- Aspartate aminotransferase (AST) =< 2.5 x ULN; if liver metastases are present, AST =< 5 x ULN
- Creatinine =< 1.25 x ULN; if > 1.25 x ULN calculated creatinine clearance must be >= 60 ml/min
- Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Provide informed written consent
- Willingness to return to NCCTG enrolling institution for follow-up
- Willingness to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study
Exclusion Criteria
Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception; note: adequate contraception must be used throughout the trial and for 8 weeks after the last dose of RAD001, by both sexes
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
History of any of the following:
- Known to be human immunodeficiency virus (HIV) positive
- Known prior/current history of hepatitis related to hepatitis B or hepatitis C
Uncontrolled intercurrent illness including, but not limited to the following:
- Ongoing or active infection (acute or chronic)
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Severely impaired lung function
- Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN (note: optimal glycemic control should be achieved before starting trial therapy)
- Liver disease such as cirrhosis or severe hepatic impairment
- Psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 4 weeks prior to registration
- Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
- Untreated brain metastases; NOTE: patients with treated, stable brain metastases for at least 12 weeks prior to study entry are eligible for enrollment
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Active, bleeding diathesis
- Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
- Currently on enzyme inducing anti-convulsants (EIACs) or other strong inducers or strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
- Current use of warfarin (Coumadin); EXCEPTION: current use of low-molecular weight heparin is allowed
- Known to be HIV positive
- Inoculated with live attenuated vaccines =< 2 weeks prior to registration; note: close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
- =< 4 weeks from major surgery; note: for this study, diagnostic laparoscopy (without other intervention) and/or biopsies (needle aspirate, core biopsy, open biopsy, etc.) are not considered major surgery
Sites / Locations
- Poudre Valley Hospital
- Front Range Cancer Specialists
- Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
- Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
- Elkhart Clinic, LLC
- Michiana Hematology-Oncology, PC - Elkhart
- Elkhart General Hospital
- St. Francis Hospital Cancer Care Services
- Howard Community Hospital
- Center for Cancer Therapy at LaPorte Hospital and Health Services
- Michiana Hematology-Oncology, PC - South Bend
- Saint Joseph Regional Medical Center
- Michiana Hematology Oncology PC - Plymouth
- Reid Hospital & Health Care Services
- CCOP - Northern Indiana CR Consortium
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC - La Porte
- McFarland Clinic, PC
- Cedar Rapids Oncology Associates
- Mercy Regional Cancer Center at Mercy Medical Center
- Medical Oncology and Hematology Associates - West Des Moines
- CCOP - Iowa Oncology Research Association
- John Stoddard Cancer Center at Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates at John Stoddard Cancer Center
- Medical Oncology and Hematology Associates at Mercy Cancer Center
- Mercy Cancer Center at Mercy Medical Center - Des Moines
- John Stoddard Cancer Center at Iowa Lutheran Hospital
- McCreery Cancer Center at Ottumwa Regional
- Siouxland Hematology-Oncology Associates, LLP
- Mercy Medical Center - Sioux City
- St. Luke's Regional Medical Center
- Cancer Center of Kansas, PA - Chanute
- Cancer Center of Kansas, PA - Dodge City
- Cancer Center of Kansas, PA - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas, PA - Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas, PA - Liberal
- Cancer Center of Kansas, PA - Newton
- Cancer Center of Kansas, PA - Parsons
- Cancer Center of Kansas, PA - Pratt
- Cancer Center of Kansas, PA - Salina
- Cancer Center of Kansas, PA - Wellington
- Associates in Womens Health, PA - North Review
- Cancer Center of Kansas, PA - Medical Arts Tower
- Cancer Center of Kansas, PA - Wichita
- CCOP - Wichita
- Via Christi Cancer Center at Via Christi Regional Medical Center
- Cancer Center of Kansas, PA - Winfield
- Hickman Cancer Center at Bixby Medical Center
- Saint Joseph Mercy Cancer Center
- CCOP - Michigan Cancer Research Consortium
- Battle Creek Health System Cancer Care Center
- Oakwood Cancer Center at Oakwood Hospital and Medical Center
- Green Bay Oncology, Limited - Escanaba
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Butterworth Hospital at Spectrum Health
- CCOP - Grand Rapids
- Lacks Cancer Center at Saint Mary's Health Care
- Van Elslander Cancer Center at St. John Hospital and Medical Center
- Dickinson County Healthcare System
- Foote Memorial Hospital
- Sparrow Regional Cancer Center
- St. Mary Mercy Hospital
- Community Cancer Center of Monroe
- Mercy Memorial Hospital - Monroe
- Mercy General Health Partners
- St. Joseph Mercy Oakland
- Mercy Regional Cancer Center at Mercy Hospital
- Spectrum Health Reed City Hospital
- Seton Cancer Institute at Saint Mary's - Saginaw
- Lakeland Regional Cancer Care Center - St. Joseph
- Lakeside Cancer Specialists, PLLC
- Munson Medical Center
- St. John Macomb Hospital
- MeritCare Bemidji
- Essentia Health - Duluth Clinic
- CCOP - Duluth
- Miller - Dwan Medical Center
- Mayo Clinic Cancer Center
- CCOP - Cancer Research for the Ozarks
- St. John's Regional Health Center
- Hulston Cancer Center at Cox Medical Center South
- CCOP - Montana Cancer Consortium
- St. Vincent Healthcare Cancer Care Services
- Hematology-Oncology Centers of the Northern Rockies - Billings
- Billings Clinic - Downtown
- Bozeman Deaconess Cancer Center
- St. James Healthcare Cancer Care
- Sletten Cancer Institute at Benefis Healthcare
- St. Peter's Hospital
- Kalispell Regional Medical Center
- Montana Cancer Specialists at Montana Cancer Center
- Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
- Medcenter One Hospital Cancer Care Center
- Mid Dakota Clinic, PC
- St. Alexius Medical Center Cancer Center
- MeritCare Broadway
- CCOP - MeritCare Hospital
- Wood County Oncology Center
- Grandview Hospital
- Good Samaritan Hospital
- David L. Rike Cancer Center at Miami Valley Hospital
- Samaritan North Cancer Care Center
- CCOP - Dayton
- Community Cancer Center
- Hematology Oncology Center
- Blanchard Valley Medical Associates
- Middletown Regional Hospital
- Wayne Hospital
- Charles F. Kettering Memorial Hospital
- Lima Memorial Hospital
- Northwest Ohio Oncology Center
- St. Charles Mercy Hospital
- Toledo Clinic - Oregon
- Flower Hospital Cancer Center
- Mercy Hospital of Tiffin
- Toledo Hospital
- St. Vincent Mercy Medical Center
- Medical University of Ohio Cancer Center
- CCOP - Toledo Community Hospital
- St. Anne Mercy Hospital
- Toledo Clinic, Incorporated - Main Clinic
- UVMC Cancer Care Center at Upper Valley Medical Center
- Fulton County Health Center
- Ruth G. McMillan Cancer Center at Greene Memorial Hospital
- Sanford Cancer Center at Sanford USD Medical Center
- Fredericksburg Oncology, Incorporated
- Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
- Green Bay Oncology, Limited at St. Mary's Hospital
- St. Mary's Hospital Medical Center - Green Bay
- St. Vincent Hospital Regional Cancer Center
- Holy Family Memorial Medical Center Cancer Care Center
- Bay Area Cancer Care Center at Bay Area Medical Center
- Green Bay Oncology, Limited - Oconto Falls
- St. Nicholas Hospital
- Green Bay Oncology, Limited - Sturgeon Bay
Arms of the Study
Arm 1
Experimental
Treatment (carboplatin, paclitaxel, and everolimus)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.