Clinical trial NCT00936702: Carboplatin, Paclitaxel, and Everolimus in Treating Patients With Previously Untreated Cancer of Unknown Primary
Official title: A Phase II Study of Carboplatin (CBDCA), Paclitaxel (TAXOL), and Everolimus (RAD001) in Previously Untreated Patients With Measurable Disease With Cancer of Unknown Primary (CUP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma of Unknown Primary Origin
Keywords: 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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-07-10
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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 and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well carboplatin given together with paclitaxel and everolimus works in treating patients with previously untreated cancer of unknown primary.

Detailed description: OBJECTIVES:

Primary

* Evaluate the response rate in patients with previously untreated cancer of unknown primary treated with the combination of carboplatin, paclitaxel, and everolimus.

Secondary

* Assess time to progression, overall survival, duration of response, and time to treatment failure in patients treated with this regimen.
* Determine adverse events of this regimen in these patients.
* Perform descriptive correlative studies to determine response of specific tumor types, identified by the Origin-FFPE test, to this regimen.

OUTLINE: This is a multicenter study.

Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive oral everolimus once daily on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients' tumor tissue samples from the most recent biopsy are analyzed for correlative studies, including gene expression profiling by Origin-FFPE test.

After completion of study therapy, patients are followed up every 3 months until disease progression, and then every 6 months for up to 3 years.

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

Primary outcomes:
measure: Percentage of Participants With Confirmed Tumor Responses
timeFrame: First 6 Cycles of treatment (an average of 6 months)
Secondary outcomes:
measure: Overall Survival
timeFrame: Time from registration to death or last follow-up (up to 3 years)
measure: Progression-free Survival
timeFrame: Time from registration to the disease progression or death (up to 3 years)
measure: Duration of Response
timeFrame: Up to 3 years
measure: Time to Treatment Failure
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Hartford
country: United States
facility: Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
state: Connecticut
city: Moline
country: United States
facility: Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
state: Illinois
city: Moline
country: United States
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic, LLC
state: Indiana
city: Elkhart
country: United States
facility: Michiana Hematology-Oncology, PC - Elkhart
state: Indiana
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Indianapolis
country: United States
facility: St. Francis Hospital Cancer Care Services
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology-Oncology, PC - South Bend
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center
state: Indiana
city: Plymouth
country: United States
facility: Michiana Hematology Oncology PC - Plymouth
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Westville
country: United States
facility: Michiana Hematology Oncology PC - La Porte
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Bettendorf
country: United States
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Regional Cancer Center at Mercy Medical Center
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Ottumwa
country: United States
facility: McCreery Cancer Center at Ottumwa Regional
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Cancer Center of Kansas, PA - Liberal
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Adrian
country: United States
facility: Hickman Cancer Center at Bixby Medical Center
state: Michigan
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital - Monroe
state: Michigan
city: Muskegon
country: United States
facility: Mercy General Health Partners
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Reed City
country: United States
facility: Spectrum Health Reed City Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Regional Cancer Care Center - St. Joseph
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeside Cancer Specialists, PLLC
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Bemidji
country: United States
facility: MeritCare Bemidji
state: Minnesota
city: Duluth
country: United States
facility: Essentia Health - Duluth Clinic
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Duluth
country: United States
facility: Miller - Dwan Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Bismarck
country: United States
facility: Medcenter One Hospital Cancer Care Center
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center Cancer Center
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Broadway
state: North Dakota
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Bowling Green
country: United States
facility: Wood County Oncology Center
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Elyria
country: United States
facility: Community Cancer Center
state: Ohio
city: Elyria
country: United States
facility: Hematology Oncology Center
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Northwest Ohio Oncology Center
state: Ohio
city: Oregon
country: United States
facility: St. Charles Mercy Hospital
state: Ohio
city: Oregon
country: United States
facility: Toledo Clinic - Oregon
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Anne Mercy Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic, Incorporated - Main Clinic
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Fredericksburg
country: United States
facility: Fredericksburg Oncology, Incorporated
state: Virginia
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Manitowoc
country: United States
facility: Holy Family Memorial Medical Center Cancer Care Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sheboygan
country: United States
facility: St. Nicholas Hospital
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Matthew P. Goetz, MD
role: STUDY_CHAIR
References:
citation: Yoon HH, Foster NR, Meyers JP, Steen PD, Visscher DW, Pillai R, Prow DM, Reynolds CM, Marchello BT, Mowat RB, Mattar BI, Erlichman C, Goetz MP. Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance). Ann Oncol. 2016 Feb;27(2):339-44. doi: 10.1093/annonc/mdv543. Epub 2015 Nov 16.