Alisertib in Treating Patients With Advanced or Metastatic Sarcoma
Status: | Completed |
---|---|
Conditions: | Ovarian Cancer, Cancer, Cancer, Cancer, Cancer, Neurology, Hematology |
Therapuetic Areas: | Hematology, Neurology, Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 12/2/2017 |
Start Date: | August 22, 2012 |
Phase II Study of MLN8237 in Advanced/Metastatic Sarcoma
This phase II trial studies how well alisertib works in treating patients with sarcoma that
has spread to other places in the body and usually cannot be cured or controlled with
treatment (advanced) or has spread to other places in the body (metastatic). Alisertib may
stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
has spread to other places in the body and usually cannot be cured or controlled with
treatment (advanced) or has spread to other places in the body (metastatic). Alisertib may
stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
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 MLN8237 (alisertib) 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 (ie, 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 every 6 months for 18 months.
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 MLN8237 (alisertib) 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 (ie, 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 every 6 months for 18 months.
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed sarcoma that is
metastatic and/or locally advanced or locally recurrent and unresectable; confirmation
of pathologic diagnosis will be performed at the registering site; 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; note: 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; note: the last dose of systemic therapy
(including tyrosine kinase inhibitors) must have been given >= 4 weeks prior to
initiation of study therapy; patients receiving BCNU or mitomycin C must have received
their last dose of such therapy at least 6 weeks prior to initiation of 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 x institutional upper limit of normal
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamate pyruvate transaminase (alanine aminotransferase [AST]) < 3 x
institutional upper limit of normal if no liver metastases or < 5 x institutional
upper limit of normal if liver metastases present
- Creatinine =< 1.5 x upper limit of normal (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; should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately; 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;
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; note: 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
- 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; note: 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. John's wort within 14 days
prior to the first dose of MLN8237 and during the study
We found this trial at
235
sites
1305 W 18th St
Sioux Falls, South Dakota 57117
Sioux Falls, South Dakota 57117
(605) 333-1000
Sanford USD Medical Center - Sioux Falls Sanford
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1 South Prospect Street
Burlington, Vermont 05401
Burlington, Vermont 05401
802-656-8990
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Bixby Medical Center ProMedica's Mission is to improve your health and well-being. Which is why,...
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McFarland Clinic PC-William R Bliss Cancer Center The William R. Bliss Cancer Center at Mary...
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Medical Center of Aurora At The Medical Center of Aurora and Centennial Medical Plaza patients...
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Sanford Clinic North-Bemidgi Sanford Health is a voluntary, not-for-profit health care organization. Through its entities,...
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Saint Vincent Healthcare The Sisters of Charity of Leavenworth, Kansas, founded St. Vincent Healthcare in...
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Boulder Community Hospital Founded in 1922 as a community-owned and operated not-for-profit hospital, Boulder Community...
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Toledo Clinic Cancer Centers-Bowling Green Our doctors evaluate and make recommendations regarding cancer treatment for...
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Bozeman Deaconess Hospital Bozeman Deaconess Hospital is a Joint Commission certified, licensed Level III trauma...
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Fairview Ridges Hospital Fairview Ridges Hospital is a 150-bed, Level III Trauma Care facility, offering...
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400 South Clark Street
Butte, Montana 59701
Butte, Montana 59701
406-723-2500
Saint James Community Hospital and Cancer Treatment Center St. James Healthcare has played an important...
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Southeast Cancer Center SoutheastHEALTH is a far-reaching network of providers and facilities including Southeast Hospital...
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Rocky Mountain Oncology Rocky Mountain Oncology Center is a spacious, comfortable, state-of-the-art 19,000 square foot...
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Cancer Center of Kansas, PA - Chanute Dr. H.E. Hynes founded Cancer Center of Kansas,...
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171 Ashley Avenue
Charleston, South Carolina 29425
Charleston, South Carolina 29425
843-792-1414
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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Mercy Cancer Center - West Lakes When it comes to cancer care, there
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Penrose-Saint Francis Healthcare Founded by the Sisters of St. Francis and the Sisters of Charity,...
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John B. Amos Cancer Center The John B. Amos Cancer Center located in Columbus, Georgia,...
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Mercy Hospital Mercy Hospital, located in Coon Rapids, Minnesota, is a 271-bed non-profit hospital that...
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Geisinger Medical Center Since 1915, Geisinger Medical Center has been known as the region’s resource...
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Miami Valley Hospital Miami Valley Hospital (MVH) is passionate about providing the most recent medical...
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Grandview Hospital You'll feel like part of our family when you visit Grandview Medical Center...
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Good Samaritan Hospital - Dayton Good Samaritan Hospital (GSH) is passionate about providing the most...
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Samaritan North Health Center Good Samaritan Hospital (GSH) is passionate about providing the most recent...
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Rose Medical Center Well known as a Denver institution and a 9th Avenue landmark for...
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Porter Adventist Hospital Founded in 1930, Porter Adventist Hospital has provided people throughout Denver and...
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1721 East 19th Ave., Suite #200 & #300
Denver, Colorado 80218
Denver, Colorado 80218
720-754-4800
Colorado Blood Cancer Institute When patients come to the Colorado Blood Cancer Institute, the entire...
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Mercy Medical Center - Des Moines Mercy Medical Center
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Iowa Methodist Medical Center Iowa Methodist Medical Center was established in 1901 in a single...
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Iowa Lutheran Hospital Iowa Lutheran Hospital has a long history of serving the Des Moines...
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Cancer Center of Kansas, PA - Dodge City Dr. H.E. Hynes founded Cancer Center of...
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Fairview Southdale Hospital Fairview Health Services is an award-winning nonprofit health care system based in...
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Cancer Center of Kansas, PA - El Dorado Dr. H.E. Hynes founded Cancer Center of...
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Green Bay Oncology - Escanaba We are one of a select few physician groups in...
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Roger Maris Cancer Center Sanford Health is an integrated health system headquartered in the Dakotas...
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Sanford Clinic North-Fargo Sanford Health is an integrated health system headquartered in the Dakotas and...
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Blanchard Valley Hospital For more than 100 years, Blanchard Valley Hospital has made quality care...
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McLeod Regional Medical Center McLeod Health, a regional presence and predominant healthcare organization, is dedicated...
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Poudre Valley Hospital A 270-bed regional medical center offering a wide array of treatments, surgeries,...
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Cancer Center of Kansas - Fort Scott Dr. H.E. Hynes founded Cancer Center of Kansas,...
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One Medical Center Drive
Franklin, Ohio 45005
Franklin, Ohio 45005
(513) 424-2111
Atrium Medical Center - Middletown Regional Hospital Atrium Medical Center (Atrium) is built on the...
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Fredericksburg Oncology Inc Fredericksburg Oncology is dedicated to offering each patient individual care and attention...
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Unity Hospital Unity Hospital is one of the Twin Cities
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Wayne Memorial Hospital Wayne Memorial Hospital, an affiliate of Wayne Health Corporation, is home to...
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1117 29th St S
Great Falls, Montana 59405
Great Falls, Montana 59405
(406) 771-7300
Benefis Healthcare- Sletten Cancer Institute Benefis Hospitals has 516 beds at its two campuses (that...
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North Colorado Medical Center NCMC is a fully accredited, private, non-profit facility licensed to operate...
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835 S. Van Buren St.
Green Bay, Wisconsin 54301
Green Bay, Wisconsin 54301
(920) 884-3135
Green Bay Oncology at Saint Vincent Hospital We are one of a select few physician...
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1726 Shawano Ave.
Green Bay, Wisconsin 54303
Green Bay, Wisconsin 54303
(920) 884-3135
Green Bay Oncology Limited at Saint Mary's Hospital We are one of a select few...
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Wayne Hospital Stretching back to our roots nearly 100 years ago, Wayne HealthCare has always...
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1319 Punahou St
Honolulu, Hawaii 96826
Honolulu, Hawaii 96826
(808) 983-6000
Kapiolani Medical Center for Women and Children Hawai‘i Pacific Health is an integrated health care...
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Queen's Medical Center The Queen's Medical Center, located in downtown Honolulu, Hawaii, is a private,...
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Straub Clinic And Hospital Founded in 1921, Straub Clinic & Hospital is a fully integrated...
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