Pixantrone Dimaleate in Treating Patients With HER2-Negative Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

Randomized Phase II Study of Two Doses of Pixantrone in Patients With Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01086605
• Other study ID #: N1031
• Secondary ID: NCCTG-N1031CDR00
• Status: Completed
• Phase: Phase 2
• Start date: May 2010
• Est. completion date: November 15, 2014

Study information

• Verified date: April 2018
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as pixantrone dimaleate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pixantrone dimaleate in different ways may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well pixantrone dimaleate works in treating patients with HER2-negative metastatic breast cancer.

Description:

OBJECTIVES:

Primary

• To assess the proportion of confirmed tumor responses at each dose level of pixantrone

Secondary

• To describe the distribution of progression-free survival (PFS) times of patients receiving pixantrone

• To assess the 6-month PFS rate in patients receiving each dose level of pixantrone

• To describe the overall survival distribution of patients receiving pixantrone

• To assess the adverse event profile of pixantrone in the treatment of patients with metastatic breast cancer.

• To evaluate the quality of life and patient-reported symptoms of patients receiving the study regimen

OUTLINE: This is a multicenter study. Patients are randomized according to prior doxorubicin treatment ( yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during study for circulating tumor cells analysis by CellSearch System and mRNA isolation assays.

Patients complete quality-of-life questionnaires using the Linear Analogue Self Assessment (LASA6) and the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) at baseline and periodically during study.

After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: November 15, 2014
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Registration and Randomization - Inclusion Criteria

1. Women or men

2. =18 years of age

3. Histologically or cytologically confirmed adenocarcinoma of the breast and clinical evidence of metastatic breast cancer.

4. Pre-treatment requirements:

4.1. Must have been previously treated in neoadjuvant, adjuvant or metastatic setting with anthracycline and/or taxane.

4.2. Must have received 2-3 prior chemotherapy treatment regimens NOTE: If NO prior (neo)adjuvant chemotherapy, patient must have received a minimum of 2 prior chemotherapy regimens in the metastatic setting.

4.2.1 NOTE: If prior (neo)adjuvant chemotherapy HAS been given, patient must have received at least 1 prior chemotherapy regimen in the metastatic setting.

4.3. Prior hormonal therapy allowed in the neo-adjuvant, adjuvant, or metastatic setting.

Unlimited prior hormonal therapy is allowed.

5. Patients must have measurable disease as defined in the protocol.

6. Negative pregnancy test done =7 days prior to registration, for women of childbearing potential only.

7. The following laboratory values obtained =15 days prior to registration.

7.1 Hemoglobin =10.0g/dL

7.2 ANC =1500/mm^3

7.3 Platelet count =100,000/mL

7.4 Total bilirubin =1.5 x ULN)

7.5 SGOT (AST) and SGPT (ALT) =5 x ULN

7.6 Serum creatinine =1.5 x ULN

8. LVEF =50% and EKG within institutional normal limits completed =22 days prior to registration.

9. ECOG Performance Status (PS) of 0, 1 or 2.

10. Life expectancy >3 months

11. Ability to complete questionnaire(s) by themselves or with assistance.

12. Patient has provided written informed consent

13. Willingness to return to NCCTG enrolling institution for follow-up.

Registration and Randomization - Exclusion Criteria

1. Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.

1.1 Pregnant women

1.2 Nursing women

1.3 Men or women of childbearing potential who are unwilling to employ adequate contraception (as determined by the treating physician)

2. Stage III or IV invasive cancer (other than breast cancer) in =3 years prior to registration (with the exception of non-melanoma skin cancer).

3. HER2 positive breast cancer (3+ by IHC or FISH amplified) breast cancer by ASCO/CAP guidelines

4. Has already received lifetime cumulative treatment with doxorubicin equivalent to >400 mg/m2.

5. >3 prior chemotherapy regimens for breast cancer.

5.1 NOTE: This number includes (neo)adjuvant chemotherapy, if given. If (neo)adjuvant chemotherapy HAS been given it counts as one (1) regimen.

6. Major surgery, chemotherapy, or immunologic therapy =3 weeks prior to registration.

6.1 NOTE: If patient has received prior treatment with bevacizumab, treatment on this trial should not begin until =4 weeks after the last dose of bevacizumab.

7. Radiotherapy =4 weeks prior to registration, except if to a non-target lesion only.

7.1 Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.

7.2 If patient receives single dose radiation for palliation or radiation to non-target lesion, they may immediately proceed to registration without waiting.

7.3 Acute adverse events from radiation must have resolved to =Grade 1 (according to current version of NCI CTCAE).

8. Evidence of active brain metastasis including leptomeningeal involvement.

8.1 CNS metastasis controlled by prior surgery and/or radiotherapy is allowed. To be considered controlled, there must be at least 2 months of no symptoms or evidence of progression prior to study entry and corticosteroid therapy given to control brain edema must have been discontinued.

9. Uncontrolled hypertension (blood pressure [BP] >160/90mmHg on =2 occasions at least 5 minutes apart). (Patients who have recently started or adjusted anti-hypertensive medications are eligible providing that BP is <140/90mmHg on any new regimen for =3 different observations in =14 days.).

10. Clinically significant cardiovascular or cerebrovascular disease, including any history of the following at any time prior to registration:

10.1 Myocardial infarction

10.2 Unstable angina pectoris

10.3 New York Heart Association (NYHA) Class II or greater congestive heart failure

10.4. Uncontrolled or clinically significant cardiac arrhythmia (patients with controlled atrial fibrillation are eligible)

11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.

12. 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.

13. History of allergy or hypersensitivity to drug product excipients or agents chemically similar to pixantrone.

14. Currently receiving treatment in a different clinical study in which investigational procedures are performed or investigational therapies are administered.

14.1 Patient may not enroll in such clinical trials while participating in this study.

Exception may be granted for trials related to symptom management (Cancer Control) which do not employ hormonal treatments or treatments that may block the path of the targeted agents used in this trial.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• pixantrone dimaleate
Given IV

Locations

Country	Name	City	State
United States	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Hematology Oncology Associates, PC	Albuquerque	New Mexico
United States	Lovelace Medical Center - Downtown	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	McFarland Clinic, PC	Ames	Iowa
United States	AnMed Cancer Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
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	Illinois CancerCare - Bloomington	Bloomington	Illinois
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. Joseph's Medical Center	Brainerd	Minnesota
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Illinois CancerCare - Canton	Canton	Illinois
United States	Illinois CancerCare - Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	Mercy Cancer Center - West Lakes	Clive	Iowa
United States	North Coast Cancer Care - Clyde	Clyde	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
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	Grady Memorial Hospital	Delaware	Ohio
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	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
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	Eureka Community Hospital	Eureka	Illinois
United States	Illinois CancerCare - Eureka	Eureka	Illinois
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	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Illinois CancerCare - Galesburg	Galesburg	Illinois
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
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	Illinois CancerCare - Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Hawaii Medical Center - East	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii
United States	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii
United States	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois
United States	Howard Community Hospital	Kokomo	Indiana
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	University of New Mexico Cancer Center - South	Las Cruces	New Mexico
United States	Kauai Medical Clinic	Lihue	Hawaii
United States	Lima Memorial Hospital	Lima	Ohio
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Illinois CancerCare - Macomb	Macomb	Illinois
United States	McDonough District Hospital	Macomb	Illinois
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
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	Illinois CancerCare - Monmouth	Monmouth	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Michiana Hematology Oncology PC - Niles	Niles	Michigan
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Illinois CancerCare - Community Cancer Center	Normal	Illinois
United States	Fisher-Titus Medical Center	Norwalk	Ohio
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	Willamette Falls Hospital	Oregon City	Oregon
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare - Pekin	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare - Peru	Peru	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
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	Adventist Medical Center	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Illinois CancerCare - Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Rutherford Hospital	Rutherfordton	North Carolina
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	Comprehensive Cancer Care, PC	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	St. Nicholas Hospital	Sheboygan	Wisconsin
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
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	Medical X-Ray Center, PC	Sioux Falls	South Dakota
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	South Bend Clinic	South Bend	Indiana
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Illinois CancerCare - Spring Valley	Spring Valley	Illinois
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Lakeview Hospital	Stillwater	Minnesota
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	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Maui Memorial Medical Center	Wailuku	Hawaii
United States	Pacific Cancer Institute - Maui	Wailuku	Hawaii
United States	St. John Macomb Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Michiana Hematology Oncology PC - La Porte	Westville	Indiana
United States	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	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 (Complete or Partial Response)	The proportion of confirmed responses will be estimated by the number of women who achieve a CR or PR on two consecutive evaluations at least 6-8 weeks apart depending on the dose level. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients at each dose level. Confidence intervals for the true success proportion at each dose level will be calculated according to the approach of Duffy and Santner. Response will be evaluated in this study using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1); Complete Response (CR): Disappearance of all non-nodal target lesions, each target lymph node must have reduction in short axis to <1.0 cm. and normalization of tumor biomarkers. Partial Response (PR): At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axis of the target lymph nodes taking as reference the Baseline Sum of Diameters.	Up to 5 years
Secondary	Time to Disease Progression	Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression one day post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier at each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).	Up to 5 years
Secondary	6-month Progression-free Survival Rate	The 6-month progression free survival (6-mo PFS) rate is the proportion of efficacy-evaluable patients progression-free 6 months from registration. The 6-mo PFS rate is defined as the total number of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of efficacy-evaluable patients enrolled on study. Patients who died without documentation of progression will be considered to have progressed on the date of their death. The true 6-mo PFS rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration at each dose level. Binomial confidence intervals for 6-mo PFS rate will be constructed for each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).	At 6 months
Secondary	Overall Survival Time	Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier at each dose level.	Up to 5 years
Secondary	Duration of Response	Duration of response is defined for all evaluable patients with measurable disease who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented at each dose level. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier at each dose level.	Up to 5 years
Secondary	Toxicity	For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of participants reporting a grade 3 or higher toxicity is reported. For a list of all reported adverse events, please refer to the Adverse Events Section below.	Up to 1 year after treatment