Carboplatin, Paclitaxel, and Everolimus in Treating Patients With Previously Untreated Cancer of Unknown Primary

Carcinoma of Unknown Primary Origin Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00936702
• Other study ID #: NCCTG-N0871
• Secondary ID: NCI-2011-01926CD
• Status: Completed
• Phase: Phase 2
• First received: July 8, 2009
• Last updated: August 11, 2016
• Start date: September 2009
• Est. completion date: August 2013

Study information

• Verified date: August 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: August 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma of Unknown Primary Origin
• Neoplasms, Unknown Primary

Intervention

Drug:
• carboplatin
Given IV
• everolimus
Given PO
• paclitaxel
Given IV

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Essentia Health - Duluth Clinic	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Elkhart Clinic, LLC	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana
United States	Community Cancer Center	Elyria	Ohio
United States	Hematology Oncology Center	Elyria	Ohio
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Wayne Hospital	Greenville	Ohio
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	St. Peter's Hospital	Helena	Montana
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	St. Francis Hospital Cancer Care Services	Indianapolis	Indiana
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	Lima Memorial Hospital	Lima	Ohio
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center	Mishawaka	Indiana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Spectrum Health Reed City Hospital	Reed City	Michigan
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	St. John Macomb Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Michiana Hematology Oncology PC - La Porte	Westville	Indiana
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of confirmed tumor responses defined to be either a CR or PR		Up to 3 years	No
Secondary	Survival time		Up to 3 years	No
Secondary	Time to disease progression		FroUp to 3 years	No
Secondary	Duration of response		Up to 3 years	No
Secondary	Time to treatment failure		Up to 3 years	Yes