Status:
WITHDRAWN
Phase 1 TheraSphere + Everolimus With Neuroendocrine Tumors (NETs) + Liver Only or Liver Dominant Disease
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborating Sponsors:
BTG International Inc.
Novartis Pharmaceuticals
Conditions:
Liver Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of the combination of everolimus with TheraSphere that can be given to patients with advanced NETs that have spread to th...
Detailed Description
Study Groups: If patient is are found to be eligible to take part in this study, they will be assigned to a dose level of everolimus based on when they joined this study. Up to 3 dose levels of evero...
Eligibility Criteria
Inclusion
- 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 tumor, 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 liver-only or liver-dominant disease.
- Patient deemed suitable for TheraSphere therapy after review of anatomic imaging by an Interventional Radiologist.
- No prior biliary enteric anastomosis.
- Intact portal vein and hepatic artery.
- Age \>/= 18 years of age.
- World Health Organization (WHO) performance status of 0 or 1.
- Patients must have normal organ and marrow function as defined below: a) leukocytes \>/= 3,000/mcL; b) absolute neutrophil count \>/= 1,500/mcL; c) hemoglobin \>/= 9 g/dL\*; d) platelets \>/= 100,000/mcL; e) total bilirubin \</= 1.5 X upper limit of normal (ULN); f) AST (SGOT) and ALT (SGPT) \</= 1.5 X institutional ULN (5x if liver function test \[LFT\] elevations due to liver metastases); g) creatinine \</= 1.5 X institutional ULN OR creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal. \*Eligibility level for hemoglobin may be reached by transfusion.
- The patient must have fasting serum glucose \</= 1.3 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.
- The effects of TheraSphere and everolimus on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use highly effective contraception from the time of study enrollment continuing for the duration of study therapy and for 8 weeks after the last dose of TheraSphere and/or everolimus. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and for 8 weeks after stopping treatment. Highly effective contraception is defined as either: 1) Total abstinence: When this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.\];
- Continuation of # 12: 2) Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; 3) Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). \[For female subjects on the study, the vasectomised male partner should be the sole partner for that subject.\]; 4) Use of a combination of any two of the following (a+b or a+c or b+c): a. Use of oral, injected, implanted or other hormonal methods of contraception; b. Placement of an intrauterine device (IUD) or intrauterine system (IUS); c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
- Continuation of # 13: In case of use of oral contraception, women should have been stable on the oral agent before taking study treatment. Sexually active males must use a condom during intercourse while taking the drug and for 8 weeks after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomised men in order to prevent delivery of the drug via seminal fluid. Female partners of male patients must also be advised to use one of the following contraception methods: Use of (1) oral, injected, implanted or other hormonal methods of contraception, or (2) intrauterine device (IUD) or intrauterine system (IUS), or (3) prior male/female sterilization.
- Women of childbearing potential must have a serum pregnancy test within 7 days prior starting study treatment.
- Patients must have at least one measurable site of disease according to RECIST in liver.
- Patients may have received prior systemic anti-neoplastic therapy. There are no limitations on the number of prior regimens. At least 28 days must have elapsed since last treatment. Prior somatostatin analogs use is allowed. The patients on 3 months of stable dose of concurrent somatostatin analogs will be allowed to continue while on study treatment.
- Patients must have international normalized ratio (INR) \</= 1.5.
Exclusion
- Patients may not be receiving any other treatment-related investigational agents.
- Uncontrolled intercurrent illness including but not limited to: a) ongoing or active infection requiring parenteral therapy at the time of study registration; b) liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class B or C) Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. Testing required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection; c) symptomatic congestive heart failure resulting in a resting O2 saturation of \< 92% on room air; d) unstable angina or pectoris myocardial infarction within 6 months of start of study drug; e) serious uncontrolled cardiac arrhythmia; f) known severely impaired lung function as defined as spirometry and 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.
- Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.).
- Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
- Patients who previously received liver directed therapy, with either radiofrequency ablation (RFA), transarterial hepatic embolization (TACE) with or without chemotherapy must have \>/= 60 days elapsed since last treatment.
- 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 of reproductive potential who are not using effective birth control methods.
- Patients with a known history of allergic reactions and/or hypersensitivity attributed compounds of similar chemical or biologic composition to 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.
- Not recovered from adverse events related to previous treatment (excluding alopecia) to active Common Terminology Criteria for Adverse Events (CTCAE) Ver. 4 \</= grade 1.
- With the exception of tumor common to a single genetic cancer syndrome (ie MEN1, MEN2, von Hippel-Lindau \[vHL\], tuberous sclerosis complex \[TSC\] etc), patients with evidence of more than one active malignancy are excluded. Active malignancy is defined as the presence of primary, regional nodal, or distant metastatic neoplasm that has not undergone definitive therapy.
- The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within 1.3 X institutional upper limit of normal and that they are on a stable dietary or therapeutic regimen for this condition.
- Patients who have received prior treatment with everolimus or an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
Key Trial Info
Start Date :
May 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
Estimated Enrollment :
Patients enrolled
Trial Details
Trial ID
NCT01864070
Start Date
May 1 2014
Last Update
July 22 2014
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