Clinical trial NCT00248287: PhII ICb With/Without Erbitux in MBC Pts
Official title: Randomized Phase II Study of Weekly Irinotecan/Carboplatin (ICb) With or Without Cetuximab (Erbitux) in Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
name: Pfizer
First posted: 2005-11-03
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the objective response rates produced by irinotecan and carboplatin therapy with or without Erbitux in patients with Metastatic Breast Cancer.


Eligibility criteria: INCLUSION CRITERIA:

Male and female patients will be eligible for inclusion in this study if they meet all of the following criteria:

* Has cytologically or pathologically confirmed, breast cancer with documented HER2+ (positive) (3+ by IHC or FISH+) or HER2- (negative) disease. ER, PR, and HER2 status must be documented in the electronic Case Report Form (eCRF) NOTE: Patients whose breast cancers are HER2 (2+) by IHC must undergo FISH testing to confirm HER2+ (positive) status.
* Has clinically confirmed Stage IV metastatic breast cancer (MBC)
* Has undergone prior Herceptin therapy if breast cancer is HER2+ (positive)
* Has measurable MBC as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

NOTE: Ascites, pleural effusion, and bone metastases are not considered measurable.

* Has had up to 1 prior chemotherapy regimens for metastatic disease. Previously untreated disease is permitted.
* Has had no prior treatment with irinotecan, carboplatin, or cisplatin
* Has an ECOG Performance Status (PS) 0-2
* Is greater than 18 years of age
* Please see protocol for specific details regarding appropriate laboratory values for inclusion to the study.
* Any prior radiation therapy has been completed \> 2 weeks prior to the start of study treatment

NOTE: Previously irradiated lesions will not be evaluable; however, these patients will still be eligible. Patients must have at least 1 measurable lesion at baseline.

* Has had a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential). A pregnancy test is also required within 7 days of Dose 1.
* If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of 6 months thereafter.
* Has signed a Patient Informed Consent Form
* Has signed a Patient Authorization Form (HIPAA)
* Has paraffin-embedded breast cancer tissue (either paraffin blocks or 20 unstained slides) available for analysis of EGFR, cytokeratin, and other biological markers. These samples will be sent to the Molecular Profiling Institute (MPI; see Appendix VII).

NOTE: Availability of samples should be confirmed prior to randomization (at latest, prior to first dose).

EXCLUSION CRITERIA:

* Has Stage I-III breast cancer or nonmeasurable metastatic breast cancer, or any disease other than that described in inclusion criterion #1
* Has received prior treatment with irinotecan, carboplatin, or cisplatin
* Is receiving any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s)
* Has received prior therapy which specifically and directly targets the EGFR pathway. Prior Herceptin is required for HER2+ patients.
* Has had prior severe infusion reaction to a monoclonal antibody
* Has received organ allograft(s) other than corneal, bone, or skin
* Has clinically significant uncontrolled cardiac disease (eg, congestive heart failure, symptomatic coronary artery disease or cardiac arrhythmias not well-controlled with medication) or has had a myocardial infarction \< 12 months
* Has ongoing peripheral neuropathy \> Grade I
* Has evidence of symptomatic or untreated central nervous system (CNS) metastases (unless CNS metastases have been irradiated). Chronic steroid treatment for the treatment of CNS metastases must have been discontinued for greater than 4 weeks prior to study enrollment.
* Has any other significant comorbidity that, in the opinion of the clinical investigator, might compromise any aspect of the study
* Has active or uncontrolled infection
* Has acute hepatitis or is known to be HIV positive
* Has a history of other malignancy within the last 5 years which could affect the diagnosis or assessment of MBC, with the exception of carcinoma of the cervix in situ, carcinoma of the bladder in situ, and basal cell carcinoma
* Has previously completed a chemotherapy regimen within 3 weeks prior to the start of study treatment, or has related toxicities unresolved prior to the start of study treatment

NOTE: If patient was receiving prior weekly or daily chemotherapy, he/she may begin study therapy 2 weeks after stopping prior therapy provided all toxicities have resolved; peripheral neuropathy must be less than Grade I as per exclusion criterion #8 above.

* Has had major surgery within 3 weeks from the start of study treatment, without complete recovery
* Has participated in any investigational drug study within 4 weeks preceding the start of study treatment
* Has received a concurrent immunotherapy or hormonal anticancer agent within 2 weeks prior to the start of the study treatment
* Is receiving a tyrosine kinase inhibitor (ie, IressaTM)
* Has had any prior stem cell or bone marrow transplant for any prior hematologic malignancy
* Is pregnant or lactating
* Is unable to comply with the requirements of the study

Primary outcomes:
measure: Objective Response Rates (ORR)
timeFrame: 2 years
Secondary outcomes:
measure: Duration of Response
timeFrame: From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 60 months.
measure: Median Time of Progression-free Survival (PFS)
timeFrame: 2 years
measure: Median Overall Survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Hematology and Oncology
state: Alabama
city: Phoenix
country: United States
facility: Hematology Oncology Asscociates
state: Arizona
city: Sedona
country: United States
facility: Northern AZ Hematology & Oncology Assoc
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Rose
state: Colorado
city: Torrington
country: United States
facility: Northwestern Connecticut Oncology Hematology Associates
state: Connecticut
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Chicago
country: United States
facility: Hematology Oncology Associates of IL
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Center
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Cancer-Southwest
state: Kansas
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Saint Louis
country: United States
facility: Arch Medical Services, Inc
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Hooksett
country: United States
facility: NH Oncology-Hematology PA
state: New Hampshire
city: Morristown
country: United States
facility: Hematology-Oncology Associates of NNJ, P.A.
state: New Jersey
city: Summit
country: United States
facility: Summit Medical Group
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Rexford
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: Rochester
country: United States
facility: Interlakes Oncology Hematology, PC
state: New York
city: Cary
country: United States
facility: Raleigh Hematology Oncology Clinic
state: North Carolina
city: Kettering
country: United States
facility: Greater Dayton Cancer Center
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Seneca
country: United States
facility: Cancer Center of the Carolinas, Seneca
state: South Carolina
city: Abilene
country: United States
facility: Texas Cancer Center-Abilene(South)
state: Texas
city: Arlington
country: United States
facility: Texas Cancer Center
state: Texas
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Beaumont
country: United States
facility: Mamie McFaddin Ward Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology, P.A. - Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Dallas
country: United States
facility: The Texas Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Denton
country: United States
facility: Texas Oncology Center - Denton
state: Texas
city: El Paso
country: United States
facility: El Paso Cancer Treatment Ctr
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Fredericksburg
country: United States
facility: San Antonio Tumor & Blood Clinic
state: Texas
city: Houston
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Longview
country: United States
facility: Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: South Texas Cancer Center-McAllen
state: Texas
city: Mesquite
country: United States
facility: Texas Cancer Center of Mesquite
state: Texas
city: Midland
country: United States
facility: Allison Cancer Center
state: Texas
city: New Braunfels
country: United States
facility: HOAST - New Braunfels
state: Texas
city: Odessa
country: United States
facility: West Texas Cancer Center
state: Texas
city: Paris
country: United States
facility: Paris Regional Cancer Center
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center-Sherman
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center-Sugar Land
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Waco
country: United States
facility: Waco Cancer Care and Research Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Salem
country: United States
facility: Onc and Hem Associates of SW VA, Inc.
state: Virginia
city: Edmonds
country: United States
facility: Puget Sound Cancer Center-Emonds
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Center-Seattle
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest-South
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists-Vancouver
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Mem Hosp/North Star Lodge
state: Washington
Study officials:
affiliation: US Oncology Research
name: Joyce A. O'Shaughnessy, MD
role: PRINCIPAL_INVESTIGATOR
References: