Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma
Phase I Study of Anti-IGF-1R Monoclonal Antibody, IMC-A12, and mTOR Inhibitor, Everolimus, in Advanced Low to Intermediate Grade Neuroendocrine Carcinoma
6 other identifiers
interventional
27
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose of cixutumumab when given together with everolimus and octreotide acetate in treating patients with advanced low- or intermediate-grade neuroendocrine cancer. Monoclonal antibodies, such as cixutumumab, may find tumor cells and help carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Octreotide acetate may interfere with the growth of tumor cells and slow the growth of neuroendocrine cancer. Giving cixutumumab together with everolimus and octreotide acetate may be a better treatment for neuroendocrine cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 16, 2010
CompletedFirst Posted
Study publicly available on registry
September 17, 2010
CompletedStudy Start
First participant enrolled
October 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2014
CompletedJuly 15, 2016
July 1, 2016
3.8 years
September 16, 2010
July 14, 2016
Conditions
Outcome Measures
Primary Outcomes (4)
Incidence of dose-limiting toxicities (DLTs) for the combination of cixutumumab and everolimus with octreotide acetate
Analysis will be performed using a patient summary of the number of cycles of study drug administered by initial dose level, and will be presented including a flag for DLTs which occurred during course 1. The recommended Phase II dose will also be presented.
21 days
Pharmacodynamic markers in blood and tumor tissue
Descriptive statistics for the changes from baseline in blood and tissue biomarkers will be presented by response category in an attempt to characterize these changes with respect to efficacy.
Up to day 1 of course 4
Pharmacokinetic parameters
Descriptive statistics will be used for plasma drug concentration data. Calculated parameters will include maximum concentration and minimum concentration.
Pre-dose and day 1 of courses 1-7
Safety profile of cixutumumab and everolimus with octreotide acetate among patients with advanced neuroendocrine tumors, defined by the incidence of adverse events
Safety data will be tabulated for all patients who receive any amount of study medication. These data will include adverse events and laboratory parameters. Adverse events will be tabulated by body system, preferred term, severity and relation to treatment. The tabulation of adverse events will be done using the CTCAE version 4.0.
Up to 30 days after completion of study treatment
Secondary Outcomes (1)
Anti-tumor activity as determined by RECIST
Up to 30 days after completion of study treatment
Other Outcomes (2)
Changes in drug-induced molecular markers
Baseline to up to day 1 of course 4
Changes in molecular markers
Baseline to up to day 1 of course 4
Study Arms (1)
Treatment (cixutumumab, octreotide acetate, everolimus)
EXPERIMENTALPatients receive cixutumumab IV over 60-90 minutes and octreotide acetate IM on day 1 and everolimus PO QD on days 1-21. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given PO
Correlative studies
Given IM
Correlative studies
Eligibility Criteria
You may qualify if:
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study
- Patients must have histologically or cytologically confirmed low or intermediate grade neuroendocrine carcinoma, for which standard curative measures do not exist; patients with neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN1) syndrome will be eligible
- Patients must have disease that is amenable to computed tomography (CT) or ultrasound (U/S) guided biopsies; patients must agree to undergo 2 biopsies; the disease identified for biopsy cannot be the only site of measurable disease
- Patients must be registered in the M.D. Anderson Cancer Center (MDACC) institutional database prior to treatment with study drug
- Zubrod performance status of 0 or 1
- Leukocytes \> 3,000/mcL
- Absolute neutrophil count \> 1,500/mcL
- Hemoglobin \> 9 g/dL; eligibility level for hemoglobin may be reached by transfusion
- Platelets \> 100,000/mcL
- Total bilirubin =\< 1.5 X upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 1.5 X institutional ULN (5 x ULN if liver function tests \[LFT\] elevations due to liver metastases)
- Creatinine =\< 1.5 X institutional ULN OR creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- The patient must have fasting serum glucose =\< 1.2 X upper limit of normal
- Fasting serum cholesterol =\< 300 mg/dL OR =\< 7.75 mmol/L AND fasting triglycerides =\< 2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
- Women of child-bearing potential and men must agree to use adequate contraception from the time of study enrollment continuing for the duration of study therapy and for 3 months after the last dose of IMC-A12 and/or everolimus; oral, implantable, or injectable contraceptives are not considered effective for this study; if barrier contraceptives are being used, these must be continued for the specified time by both sexes; women are considered to be of child-bearing potential if they have not undergone surgical sterilization (laparoscopic tubal ligation, hysterectomy, bilateral salping-oophorectomy) or have not reached menopause, defined as amenorrhea persisting for at least twelve consecutive months; men of any age are considered to be fertile unless they have undergone bilateral vasectomy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; if the subject becomes pregnant while on study, she must discontinue study treatment
- +7 more criteria
You may not qualify if:
- Patients may not be receiving any other investigational agents
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection requiring parenteral therapy at the time of study registration
- Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C); note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients
- Symptomatic congestive heart failure resulting in a resting oxygen saturation of \< 92% on room air
- Unstable angina or pectoris myocardial infarction within 6 months of start of study drug
- Serious uncontrolled cardiac arrhythmia
- Known severely impaired lung function as defined as spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or oxygen saturation that is 88% or less at rest on room air; pulmonary function test (PFT) is not required at study entry
- A known history of human immunodeficiency virus (HIV) seropositivity
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; pregnant women are excluded from the study; breastfeeding women should be excluded
- Patients with a known history of allergic reactions and/or hypersensitivity attributed compounds of similar chemical or biologic composition to IMC-A12, everolimus or other rapamycins (sirolimus, temsirolimus)
- Known history of brain or leptomeningeal metastases
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
- Patients who have had hormonal therapy (other than replacement) within 4 weeks prior to entering the study
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Dasari A, Phan A, Gupta S, Rashid A, Yeung SC, Hess K, Chen H, Tarco E, Chen H, Wei C, Anh-Do K, Halperin D, Meric-Bernstam F, Yao J. Phase I study of the anti-IGF1R antibody cixutumumab with everolimus and octreotide in advanced well-differentiated neuroendocrine tumors. Endocr Relat Cancer. 2015 Jun;22(3):431-41. doi: 10.1530/ERC-15-0002. Epub 2015 Apr 21.
PMID: 25900182DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
James Yao
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 16, 2010
First Posted
September 17, 2010
Study Start
October 1, 2010
Primary Completion
July 1, 2014
Last Updated
July 15, 2016
Record last verified: 2016-07