Trial Title:
Cabozantinib S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer
NCT ID:
NCT01935934
Condition:
Endometrial Adenosquamous Carcinoma
Endometrial Clear Cell Adenocarcinoma
Endometrial Mixed Cell Adenocarcinoma
Endometrial Serous Adenocarcinoma
Metastatic Endometrioid Adenocarcinoma
Recurrent Uterine Corpus Cancer
Stage IV Uterine Corpus Cancer AJCC v7
Stage IVA Uterine Corpus Cancer AJCC v7
Stage IVB Uterine Corpus Cancer AJCC v7
Uterine Corpus Carcinosarcoma
Conditions: Official terms:
Adenocarcinoma
Endometrial Neoplasms
Cystadenocarcinoma, Serous
Carcinoma, Endometrioid
Carcinosarcoma
Adenocarcinoma, Clear Cell
Carcinoma, Adenosquamous
Recurrence
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cabozantinib S-malate
Description:
Given PO
Arm group label:
Treatment (cabozantinib s-malate)
Other name:
BMS-907351
Other name:
Cabometyx
Other name:
Cometriq
Other name:
XL 184
Other name:
XL-184
Other name:
XL184
Intervention type:
Other
Intervention name:
Laboratory Biomarker Analysis
Description:
Correlative studies
Arm group label:
Treatment (cabozantinib s-malate)
Intervention type:
Other
Intervention name:
Pharmacological Study
Description:
Correlative studies
Arm group label:
Treatment (cabozantinib s-malate)
Summary:
This phase II trial studies how well cabozantinib s-malate works in treating patients
with endometrial cancer that has come back (recurrent) or has spread to other places in
the body (metastatic). Cabozantinib s-malate 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.
Detailed description:
PRIMARY OBJECTIVES:
I. Determine efficacy of single agent cabozantinib s-malate (cabozantinib) in women
previously receiving one line of chemotherapy for metastatic endometrial cancer or with
progression within 12 months of completing adjuvant therapy, with co-primary endpoints of
objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and
progression-free-survival at 12 weeks (PFS).
SECONDARY OBJECTIVES:
I. Correlation of clinical response with baseline molecular status of archival tumor
(hepatocyte growth factor receptor [c-met] amplification & mutation status) and overall
survival.
OUTLINE:
Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4 weeks or every 6
months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed metastatic endometrial
cancer; eligible histologies for the experimental cohort are: endometrioid or
serous; eligible histologies for the exploratory cohort are: carcinosarcoma, clear
cell, mixed, adenosquamous and any other rare sub-type of endometrial cancer
- Patients must have measurable disease, 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 >= 10 mm with computed
tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
and >= 15 mm in short axis for nodal lesions; patients must have radiographic
evidence of disease progression following the most recent line of treatment
- Prior therapy: Eligible subjects must have had 1 line of systemic cytotoxic
treatment; this may be adjuvant therapy with documented progression within 12 months
of completion, or 1 line of cytotoxic therapy for metastatic disease; NOTE: eligible
patients are allowed up to 2 lines of systemic cytotoxic treatment, of which only 1
line is allowed for metastatic disease; the acceptance of progression within 12
months of adjuvant is part inclusion to not require patient to re-challenge with
chemotherapy (chemo) if they progressed soon after adjuvant therapy; prior hormonal
therapy for metastatic/recurrent disease is also allowed; prior targeted therapy not
directed against cMET or vascular endothelial growth factor (VEGF) pathways is
allowed
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 3 months
- Absolute neutrophil count >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 3.0 X institutional upper limit of normal
- Creatinine =< 1.5 x ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients
with creatinine levels above institutional normal
- Hemoglobin >= 90 g/L
- Serum albumin >= 28 g/L
- Lipase < 2.0 x ULN; no radiologic/clinical evidence of pancreatitis
- Urine protein/creatinine ratio (UPCR) =< 1
- Serum phosphorus, calcium, magnesium and potassium >= lower limit of normal (LLN)
- Women of childbearing potential must have a negative pregnancy test at screening;
women of childbearing potential include women who have experienced menarche and who
have not undergone successful surgical sterilization (hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopausal is
defined as amenorrhea >= 12 consecutive months; note: women who have been
amenorrheic for 12 or more months are still considered to be of childbearing
potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens,
ovarian suppression or any other reversible reason
- Women of child-bearing potential must agree to use adequate contraception prior to
study entry and for the duration of study participation; should a woman become
pregnant or suspect she is pregnant while she is participating in this study, she
should inform her treating physician immediately; sexually active subjects must
agree to use medically accepted barrier methods of contraception (e.g., male or
female condom) during the course of the study and for 4 months after the last dose
of study drug(s), even if oral contraceptives are also used; all subjects of
reproductive potential must agree to use both a barrier method and a second method
of birth control during the course of the study and for 4 months after the last dose
of study drug(s)
- Patients must consent to analysis on archival tissue; if archival sample is not
available, a sufficient tumor biopsy can be performed a minimum of 28 days prior to
start of treatment if felt to be clinically reasonable
- Ability to understand and the willingness to sign a written informed consent
document
Exclusion Criteria:
- Patients who have had chemotherapy (including investigational cytotoxic
chemotherapy), biologic agents (e.g., cytokines or antibodies) or radiotherapy
within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before the first dose of
study treatment or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier
- Prior treatment with cabozantinib
- The subject has received radiation therapy:
- To bone metastasis within 14 days before the first dose of study treatment
- To any other site(s) within 28 days before the first dose of study treatment
- The subject has received radionuclide treatment within 6 weeks of the first dose of
study treatment
- The subject has received prior treatment with a small molecule kinase inhibitor or a
hormonal therapy (including investigational kinase inhibitors or hormones) within 14
days or five half-lives of the compound or active metabolites, whichever is longer,
before the first dose of study treatment
- The subject has received any other type of investigational agent within 28 days
before the first dose of study treatment
- The subject has not recovered to baseline or Common Terminology Criteria for Adverse
Events (CTCAE) =< grade 1 from related toxicity to all prior therapies except
alopecia and other non-clinically significant adverse events (AEs)
- Any other prior malignancy from which the patient has been disease free for less
than 3 years, with the exception of adequately treated and cured basal or squamous
cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any
other cancer
- Patients with known brain metastases should be excluded from this clinical trial
- The subject has prothrombin time (PT)/international normalized ratio (INR) or
partial thromboplastin time (PTT) test >= 1.3 x the laboratory ULN =< 7 days before
the first dose of study treatment
- Therapeutic anticoagulation with warfarin, antiplatelet agents (e.g., clopidogrel),
thrombin, or Factor Xa inhibitors is not allowed; therapeutic anticoagulation with
low molecular weight heparin (LMWH) is allowed as well as prophylactic
anticoagulation using low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1
mg/day), and LMWH
- The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g.,
dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine,
phenobarbital, and St. John's wort)
- The subject has experienced any of the following:
- Clinically-significant gastrointestinal bleeding within 6 months before the
first dose of study treatment
- Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the
first dose of study treatment
- Any other signs indicative of pulmonary hemorrhage within 3 months before the
first dose of study treatment
- The subject has tumor in contact with, invading or encasing any major blood vessels
- The subject has evidence of tumor invading the gastrointestinal (GI) tract
(esophagus, stomach, small or large bowel, rectum or anus), or any evidence of
endotracheal or endobronchial tumor within 28 days before the first dose of
cabozantinib
- The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:
- Cardiovascular disorders including:
- Congestive heart failure (CHF): New York Heart Association (NYHA) class
III (moderate) or class IV (severe) at the time of screening
- Concurrent uncontrolled hypertension defined as sustained blood pressure
(BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal
antihypertensive treatment within 7 days of the first dose of study
treatment
- Any history of congenital long QT syndrome
- Any of the following within 6 months before the first dose of study
treatment:
- Unstable angina pectoris
- Clinically-significant cardiac arrhythmias
- Stroke (including transient ischemic attack [TIA], or other ischemic
event)
- Myocardial infarction
- Thromboembolic event requiring therapeutic anticoagulation (note:
subjects with a venous filter [e.g. vena cava filter] are not
eligible for this study)
- Gastrointestinal disorders particularly those associated with a high risk of
perforation or fistula formation including:
- Any of the following within 28 days before the first dose of study treatment
- Intra-abdominal tumor/metastases invading GI mucosa
- Active peptic ulcer disease,
- Inflammatory bowel disease (including ulcerative colitis and Crohn's
disease), diverticulitis, cholecystitis, symptomatic cholangitis or
appendicitis
- Malabsorption syndrome
- Any of the following within 6 months before the first dose of study treatment:
- Abdominal fistula
- Gastrointestinal perforation
- Bowel obstruction or gastric outlet obstruction
- Intra-abdominal abscess; note: complete resolution of an intra-abdominal
abscess must be confirmed prior to initiating treatment with cabozantinib
even if the abscess occurred more than 6 months before the first dose of
study treatment
- Other disorders associated with a high risk of fistula formation including
percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the
first dose of study therapy
- Other clinically significant disorders such as:
- Active uncontrolled infection requiring intravenous systemic treatment within
14 days before the first dose of study treatment
- Serious non-healing wound/ulcer/bone fracture within 28 days before the first
dose of study treatment
- History of organ transplant
- Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days
before the first dose of study treatment
- History of major surgery as follows:
- Major surgery within 3 months of the first dose of cabozantinib if there
were no wound healing complications or within 6 months of the first dose
of cabozantinib if there were wound complications
- Minor surgery within 1 month of the first dose of cabozantinib if there
were no wound healing complications or within 3 months of the first dose
of cabozantinib if there were wound complications
- In addition, complete wound healing from prior surgery must be
confirmed at least 28 days before the first dose of cabozantinib
irrespective of the time from surgery
- The subject is unable to swallow tablets
- The subject has a corrected QT interval calculated by the Fridericia formula (QTcF)
> 500 ms =< 7 days before the first dose of study treatment
- The subject is unable or unwilling to abide by the study protocol or cooperate fully
with the investigator or designee
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to XL184
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with XL184
- Known human immunodeficiency virus (HIV)-positive patients on combination
antiretroviral therapy are ineligible
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Comprehensive Cancer Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Facility:
Name:
Los Angeles General Medical Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Facility:
Name:
USC / Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Facility:
Name:
City of Hope South Pasadena
Address:
City:
South Pasadena
Zip:
91030
Country:
United States
Facility:
Name:
University of Chicago Comprehensive Cancer Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Facility:
Name:
Decatur Memorial Hospital
Address:
City:
Decatur
Zip:
62526
Country:
United States
Facility:
Name:
NorthShore University HealthSystem-Evanston Hospital
Address:
City:
Evanston
Zip:
60201
Country:
United States
Facility:
Name:
Southern Illinois University School of Medicine
Address:
City:
Springfield
Zip:
62702
Country:
United States
Facility:
Name:
Indiana University/Melvin and Bren Simon Cancer Center
Address:
City:
Indianapolis
Zip:
46202
Country:
United States
Facility:
Name:
University of Michigan Comprehensive Cancer Center
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Facility:
Name:
Fox Chase Cancer Center
Address:
City:
Philadelphia
Zip:
19111
Country:
United States
Facility:
Name:
UPMC-Magee Womens Hospital
Address:
City:
Pittsburgh
Zip:
15213
Country:
United States
Facility:
Name:
Tom Baker Cancer Centre
Address:
City:
Calgary
Zip:
T2N 4N2
Country:
Canada
Facility:
Name:
Cross Cancer Institute
Address:
City:
Edmonton
Zip:
T6G 1Z2
Country:
Canada
Facility:
Name:
Juravinski Cancer Centre at Hamilton Health Sciences
Address:
City:
Hamilton
Zip:
L8V 5C2
Country:
Canada
Facility:
Name:
Kingston Health Sciences Centre
Address:
City:
Kingston
Zip:
K7L 2V7
Country:
Canada
Facility:
Name:
London Regional Cancer Program
Address:
City:
London
Zip:
N6A 4L6
Country:
Canada
Facility:
Name:
Ottawa Hospital and Cancer Center-General Campus
Address:
City:
Ottawa
Zip:
K1H 8L6
Country:
Canada
Facility:
Name:
University Health Network-Princess Margaret Hospital
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Start date:
April 29, 2013
Completion date:
March 26, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01935934
