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Phase II Study of MLN8237 in Advanced / Metastatic Sarcoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Alveolar Soft-part Sarcoma, Adult Angiosarcoma, Adult Epithelioid Sarcoma, Adult Extraskeletal Chondrosarcoma, Adult Fibrosarcoma, Adult Leiomyosarcoma, Adult Liposarcoma, Adult Neurofibrosarcoma, Chondrosarcoma, Endometrial Stromal Sarcoma, Mast Cell Sarcoma, Metastatic Adult Malignant Fibrous Histiocytoma of Bone, Ovarian Carcinosarcoma, Ovarian Sarcoma, Recurrent Adult Malignant Fibrous Histiocytoma of Bone, Recurrent Adult Soft Tissue Sarcoma, Small Intestine Leiomyosarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma

Thank you

Trial Information

Phase II Study of MLN8237 in Advanced / Metastatic Sarcoma


PRIMARY OBJECTIVES:

I. To determine the response rate (complete response [CR] + partial response [PR]) assessed
for patients within each cohort: liposarcoma (cohort 1); leiomyosarcoma (non-uterine)
(cohort 2); undifferentiated sarcoma (including pleomorphic undifferentiated sarcoma,
formerly known as malignant fibrous histiocytoma, and myxofibrosarcoma) (cohort 3);
malignant peripheral nerve sheath tumor (cohort 4); and other sarcomas (cohort 5).

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival (OS) for patients
treated with alisertib (MLN8237) in each cohort.

II. To assess the adverse events associated with patients treated with MLN8237 in each
cohort.

TERTIARY OBJECTIVES:

I. To correlate potential clinical benefit with markers of aurora kinase inhibition in pre-
and post-treatment tumor biopsies.

II. To correlate clinical outcome with change in fluorine F 18 fluorothymidine
(FLT)-positron emission tomography (PET) uptake at baseline versus after one week of
treatment (i.e., week 2 of cycle 1).

OUTLINE:

Patients receive alisertib orally (PO) twice daily (BID) on days 1-7. Courses repeat every
21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 18 months.


Inclusion Criteria:



- Patients must have histologically or cytologically confirmed sarcoma that is
metastatic and/or locally advanced or locally recurrent and unresectable

- Patients will been rolled on one of five cohorts of the study:

- Cohort 1: Liposarcoma

- Cohort 2: Leiomyosarcoma (non-uterine)

- Cohort 3: Undifferentiated sarcoma (including malignant fibrous
histiocytoma and myxofibrosarcoma)

- Cohort 4: Malignant peripheral nerve sheath tumor

- Cohort 5: Other sarcomas

- Patients must have measurable disease per Response Evaluation Criteria in Solid
Tumors(RECIST) 1.1, defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded for non-nodal lesions and
short axis for nodal lesions) as ≥ 2 cm with conventional techniques or as ≥ 1 cm
with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or
calipers by clinical exam

- Any number of prior therapies is permitted

- The last dose of systemic therapy (including tyrosine kinase inhibitors) must
have been given ≥ 4 weeks prior to initiation of study therapy

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelet count >= 100,000/mcL

- Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamic pyruvate transaminase (alanine aminotransferase [AST]) < 3 times ULN
if no liver metastases or < 5 times ULN if liver metastases present

- Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73m^2 for patients
with creatinine levels above institutional normal

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; men treated or enrolled on this protocol
must also agree to use adequate contraception prior to the study, for the duration of
study participation, and 4 months after completion of MLN8237 administration

- Ability to understand and the willingness to sign a written informed consent document

- According to current guidelines, patients must be able to take oral medication and to
maintain a fast as required for approximately one hour before and two hours after
MLN8237 administration

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- No patients who have had radiation therapy to more than 25% of the bone marrow
(whole pelvic radiation is considered to be over 25%)

- Patients who are receiving any other investigational agents

- Patients with known brain metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to MLN8237 including, but not limited to, established allergic reaction
to benzodiazepines

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, New York Heart Association (NYHA) class II-IV heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements

- Pregnant women; women of child-bearing potential must have a negative serum or urine
pregnancy test within 7 days prior to registration; breastfeeding should be
discontinued if the mother is treated with MLN8237; these potential risks may also
apply to other agents used in this study

- Leiomyosarcoma of the uterus

- Patients known to be human immunodeficiency virus (HIV)-positive on antiretroviral
therapy

- Prior allogeneic bone marrow or organ transplantation

- Known history of uncontrolled sleep apnea syndrome and other conditions that could
result in excessive daytime sleepiness such as severe chronic obstructive pulmonary
disease, requirement for supplemental oxygen, or any conditions that could result in
excessive toxicity associated with the benzodiazepine-like effects of MLN8237

- Requirement for constant administration of proton pump inhibitor, histamine-2 (H2)
antagonist, or pancreatic enzymes

- Intermittent uses of antacids or H2 antagonists are allowed

- Inability to swallow oral medication or to maintain a required fast for approximately
one hour before and two hours after MLN8237 administration or any condition that
would modify small bowel absorption of oral medications, including malabsorption or
resection of pancreas or upper bowel

- Treatment with clinically significant enzyme inducers, such as the enzyme-inducing
antiepileptic drugs phenytoin, carbamazepine, oxcarbazepine, primidone or
phenobarbital, or rifampin, rifabutin, rifapentine, or St. Johns wort within 14 days
prior to the first dose of MLN8237 and during the study

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

The confirmed response rate (CR/PR)

Outcome Description:

The overall response rate (CR + PR) will be estimated and a 90% confidence interval provided.

Outcome Time Frame:

Up to 18 months

Safety Issue:

No

Principal Investigator

Mark Dickson

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01991

NCT ID:

NCT01653028

Start Date:

August 2012

Completion Date:

Related Keywords:

  • Adult Alveolar Soft-part Sarcoma
  • Adult Angiosarcoma
  • Adult Epithelioid Sarcoma
  • Adult Extraskeletal Chondrosarcoma
  • Adult Fibrosarcoma
  • Adult Leiomyosarcoma
  • Adult Liposarcoma
  • Adult Neurofibrosarcoma
  • Chondrosarcoma
  • Endometrial Stromal Sarcoma
  • Mast Cell Sarcoma
  • Metastatic Adult Malignant Fibrous Histiocytoma of Bone
  • Ovarian Carcinosarcoma
  • Ovarian Sarcoma
  • Recurrent Adult Malignant Fibrous Histiocytoma of Bone
  • Recurrent Adult Soft Tissue Sarcoma
  • Small Intestine Leiomyosarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Histiocytoma
  • Histiocytoma, Benign Fibrous
  • Carcinosarcoma
  • Mixed Tumor, Mullerian
  • Chondrosarcoma
  • Fibrosarcoma
  • Fibrosis
  • Hemangiosarcoma
  • Leiomyosarcoma
  • Liposarcoma
  • Mast-Cell Sarcoma
  • Sarcoma
  • Sarcoma, Endometrial Stromal
  • Sarcoma, Alveolar Soft Part
  • Neurofibrosarcoma
  • Neurilemmoma
  • Adenoma
  • Histiocytoma, Malignant Fibrous
  • Ovarian Neoplasms

Name

Location

Memorial Sloan Kettering Cancer Center New York, New York  10021
Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic Rochester, Minnesota  55905
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
Washington University School of Medicine Saint Louis, Missouri  63110
Medical University of South Carolina Charleston, South Carolina  29425-0721
Boulder Community Hospital Boulder, Colorado  80301-9019
Porter Adventist Hospital Denver, Colorado  80210
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
Sky Ridge Medical Center Lone Tree, Colorado  80124
Fairview Ridges Hospital Burnsville, Minnesota  55337
Hutchinson Area Health Care Hutchinson, Minnesota  55350
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Loyola University Medical Center Maywood, Illinois  60153
CentraCare Clinic Saint Cloud, Minnesota  56303
Boston Medical Center Boston, Massachusetts  02118
University of Nebraska Medical Center Omaha, Nebraska  68198-3330
Via Christi Regional Medical Center Wichita, Kansas  67214
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
Iowa Methodist Medical Center Des Moines, Iowa  50309
Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Cancer Center of Kansas - Chanute Chanute, Kansas  66720
Cancer Center of Kansas - Dodge City Dodge City, Kansas  67801
Cancer Center of Kansas - Newton Newton, Kansas  67114
Cancer Center of Kansas - Salina Salina, Kansas  67042
Cancer Center of Kansas - Wellington Wellington, Kansas  67152
Associates in Womens Health Wichita, Kansas  67203
Cancer Center of Kansas - Winfield Winfield, Kansas  67156
Bozeman Deaconess Hospital Bozeman, Montana  59715
Kalispell Regional Medical Center Kalispell, Montana  59901
Methodist Estabrook Cancer Center Omaha, Nebraska  68114-4199
Poudre Valley Hospital Fort Collins, Colorado  80524
Community Cancer Center of Monroe Monroe, Michigan  48162
Grandview Hospital Dayton, Ohio  45405
Lima Memorial Hospital Lima, Ohio  45804
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Fulton County Health Center Wauseon, Ohio  43567
Mountainview Medical Berlin, Vermont  05602
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Mercy Hospital Coon Rapids, Minnesota  55433
Medical Oncology and Hematology Associates Des Moines, Iowa  50309
Bixby Medical Center Adrian, Michigan  49221
Fairview-Southdale Hospital Edina, Minnesota  55435
Abbott-Northwestern Hospital Minneapolis, Minnesota  55407
Regions Hospital Saint Paul, Minnesota  55101
Saint Francis Regional Medical Center Shakopee, Minnesota  55379
Rice Memorial Hospital Willmar, Minnesota  56201
Miami Valley Hospital Dayton, Ohio  45409
Cancer Center of Kansas - Fort Scott Fort Scott, Kansas  66701
Cancer Center of Kansas-Independence Independence, Kansas  67301
Lawrence Memorial Hospital Lawrence, Kansas  66044
Menorah Medical Center Overland Park, Kansas  66209
North Kansas City Hospital Kansas City, Missouri  64116
Research Medical Center Kansas City, Missouri  64132
Saint Luke's East - Lee's Summit Lee's Summit, Missouri  64086
Wayne Hospital Greenville, Ohio  45331
Longmont United Hospital Longmont, Colorado  80501
Greene Memorial Hospital Xenia, Ohio  45385
Mayo Clinic in Arizona Scottsdale, Arizona  85259-5404
Saint Francis Medical Center Grand Island, Nebraska  68802
McLeod Regional Medical Center Florence, South Carolina  29501
Queen's Medical Center Honolulu, Hawaii  96813
Northwestern University Chicago, Illinois  60611
Kapiolani Medical Center at Pali Momi Aiea, Hawaii  96701
Kapiolani Medical Center for Women and Children Honolulu, Hawaii  96826
Hennepin County Medical Center Minneapolis, Minnesota  
Glens Falls Hospital Glens Falls, New York  12801
Straub Clinic and Hospital Honolulu, Hawaii  96813
University Of Vermont Burlington,, Vermont  05403
Presbyterian - Saint Lukes Medical Center - Health One Denver, Colorado  80218
Wichita CCOP Wichita, Kansas  67214-3882
Montana Cancer Consortium CCOP Billings, Montana  59101
Flower Hospital Sylvania, Ohio  43560-2197
Huntsman Cancer Institute/University of Utah Salt Lake City, Utah  84112
Metro-Minnesota CCOP St. Louis Park, Minnesota  
Lakeview Hospital Stillwater, Minnesota  55082
Montana Cancer Specialists Missoula, Montana  59807-7877
Castle Medical Center Kailua, Hawaii  96734
Southeast Cancer Center Cape Girardeau, Missouri  63703
Froedtert and the Medical College of Wisconsin Milwaukee, Wisconsin  53226
The Medical Center of Aurora Aurora, Colorado  80012
Penrose-Saint Francis Healthcare Colorado Springs, Colorado  80907
Saint Anthony Central Hospital Denver, Colorado  80204
Exempla Saint Joseph Hospital Denver, Colorado  80218
Colorado Cancer Research Program CCOP Denver, Colorado  80224-2522
Saint Mary Corwin Medical Center Pueblo, Colorado  81004
John B Amos Cancer Center Columbus, Georgia  31904
Oncare Hawaii Inc-POB II Honolulu, Hawaii  96813
Oncare Hawaii Inc-Kuakini Honolulu, Hawaii  96817
University of Hawaii Honolulu, Hawaii  96813
Reid Hospital and Health Care Services Richmond, Indiana  47374
McFarland Clinic Ames, Iowa  50010
Medical Oncology and Hematology Associates-West Des Moines Clive, Iowa  50325
Iowa Oncology Research Association CCOP Des Moines, Iowa  50309
Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des Moines Des Moines, Iowa  50309
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Cancer Center of Kansas - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas-Kingman Kingman, Kansas  67068
Cancer Center of Kansas - Parsons Parsons, Kansas  67357
Cancer Center of Kansas - Pratt Pratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas - Main Office Wichita, Kansas  67214
Hickman Cancer Center Adrian, Michigan  49221
Green Bay Oncology - Escanaba Escanaba, Michigan  49431
Green Bay Oncology - Iron Mountain Iron Mountain, Michigan  49801
Mercy Memorial Hospital Monroe, Michigan  48162
Unity Hospital Fridley, Minnesota  55432
Saint John's Hospital - Healtheast Maplewood, Minnesota  55109
Minnesota Oncology Hematology PA-Maplewood Maplewood, Minnesota  55109
North Memorial Medical Health Center Robbinsdale, Minnesota  55422
Saint Cloud Hospital Saint Cloud, Minnesota  56303
Park Nicollet Clinic - Saint Louis Park Saint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-Woodbury Woodbury, Minnesota  55125
Saint Luke's Hospital of Kansas City Kansas City, Missouri  64111
Missouri Baptist Medical Center Saint Louis, Missouri  63131
Hematology-Oncology Centers of the Northern Rockies PC Billings, Montana  59101
Saint Vincent Healthcare Billings, Montana  59101
Billings Clinic Billings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment Center Butte, Montana  59701
Benefis Healthcare- Sletten Cancer Institute Great Falls, Montana  59405
Saint Peter's Community Hospital Helena, Montana  59601
Saint Patrick Hospital - Community Hospital Missoula, Montana  59802
Wayne Memorial Hospital Goldsboro, North Carolina  27534
Good Samaritan Hospital - Dayton Dayton, Ohio  45406
Dayton CCOP Dayton, Ohio  45429
Samaritan North Health Center Dayton, Ohio  45415
Hematology Oncology Center Incorporated Elyria, Ohio  44035
Blanchard Valley Hospital Findlay, Ohio  45840
Atrium Medical Center-Middletown Regional Hospital Franklin, Ohio  45005-1066
Kettering Medical Center Kettering, Ohio  45429
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee, Ohio  43537
Saint Charles Hospital Oregon, Ohio  43616
Toledo Community Hospital Oncology Program CCOP Toledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy Hospital Toledo, Ohio  43623
University of Toledo Toledo, Ohio  43614
Saint Vincent Mercy Medical Center Toledo, Ohio  43608
Upper Valley Medical Center Troy, Ohio  45373
Wright-Patterson Medical Center Wright-Patterson Afb, Ohio  45433-5529
Natalie W Bryant Cancer Center Tulsa, Oklahoma  74136
Sanford Cancer Center-Oncology Clinic Sioux Falls, South Dakota  57104
Fredericksburg Oncology Inc Fredericksburg, Virginia  22401
Saint Vincent Hospital Green Bay, Wisconsin  54301
Green Bay Oncology Limited at Saint Mary's Hospital Green Bay, Wisconsin  54303
Saint Mary's Hospital Green Bay, Wisconsin  54303
Green Bay Oncology at Saint Vincent Hospital Green Bay, Wisconsin  54301-3526
Bay Area Medical Center Marinette, Wisconsin  54143
Green Bay Oncology - Oconto Falls Oconto Falls, Wisconsin  54154
Green Bay Oncology - Sturgeon Bay Sturgeon Bay, Wisconsin  54235
Memorial Healthcare System - Joe DiMaggio Children's Hospital Hollywood, Florida  33021
Cancer Center of Kansas-Liberal Liberal, Kansas  67901
UMDNJ - New Jersey Medical School Newark, New Jersey  07103
Community Health Partners Regional Medical Center Elyria, Ohio  44035
Holy Family Memorial Hospital Manitowoc, Wisconsin  54221
Wilcox Memorial Hospital and Kauai Medical Clinic Lihue, Hawaii  96766-1099
Saint Luke's South Hospital Overland Park, Kansas  66213
Kansas City CCOP Prairie Village, Kansas  66208
Capital Region Medical Center-Goldschmidt Cancer Center Jefferson City, Missouri  65109
Heartland Hematology and Oncology Associates Incorporated Kansas City, Missouri  64118
Saint Joseph Oncology Inc Saint Joseph, Missouri  64507
Saint Nicholas Hospital Madison, Wisconsin  53715
Siouxland Hematology Oncology Associates Sioux City, Iowa  51101
Methodist West Hospital West Des Moines, Iowa  50266-7700
Carle Foundation - Carle Cancer Center Urbana, Illinois  61801
Sanford Clinic North-Fargo Fargo, North Dakota  58102
Franciscan St. Francis Health Indianapolis, Indiana  46237
The Toledo Hospital/Toledo Children's Hospital Toledo, Ohio  43606
Sanford USD Medical Center - Sioux Falls Sioux Falls, South Dakota  57117-5134
Sanford Clinic North-Bemidgi Bemidji, Minnesota  56601
Toledo Clinic Cancer Centers-Oregon Oregon, Ohio  43616
Memorial Sloan-Kettering Cancer Center at Suffolk Commack, New York  11725
Toledo Clinic Cancer Centers-Bowling Green Bowling Green, Ohio  43402
Toledo Clinic Cancer Centers-Maumee Maumee, Ohio  43537-1839
Toledo Clinic Cancer Centers-Toledo Toledo, Ohio  43623
Mercy Cancer Center-West Lakes Clive, Iowa  50325
Mercy Medical Center-West Lakes West Des Moines, Iowa  50266
Oncare Hawaii Inc - Kapiolani Medical Center at Pali Momi Aiea, Hawaii  96701