AzTrials
AzTrials

Neuroendocrine TumorsPhase 1NCT01469572

Pasireotide, Everolimus and Selective Internal Radioembolization Therapy for Unresectable Hepatic Metastases

A Phase 1 study testing Pasireotide, Sir-sphere Radioembolization and Everolimus in people with Neuroendocrine Tumors, run by Emory University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to see the safety and activity of using pasireotide, everolimus and radioembolization (Selective Internal Radioembolization Therapy-SIRT) in the treatment of neuroendocrine tumors (carcinoid) that has spread to the liver. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Tumors
What is being tested?
Pasireotide, Sir-sphere Radioembolization and Everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Dec 2011to Oct 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed low to intermediate grade neuroendocrine tumors with unresectable liver metastasis
  • Patients must have evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) despite optimal octreotide therapy (octreotide long acting release [LAR] 30 mg every month)
  • Prior treatment permitted include: surgery, prior systemic therapies (≤ 2 prior lines of chemotherapy), or radiation therapy
  • Patients must have measurable disease by RECIST 1.1 criteria
  • For the patients in the phase Ib study, neuroendocrine tumor must involve both liver lobes
  • Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy)
Show all 20Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Adequate bone marrow function as shown by:
  • Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L
  • Platelets greater than or equal to 100 x 10^9/L
  • Hb greater than 9 g/dL
  • Adequate liver function as shown by:
  • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x ULN (≤ 3x ULN in patients with liver metastases)
  • International normalized ratio (INR) ≤ 1.5 (anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin)
  • Patient receiving low molecular weight (LMW) heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level < 1.1 U/mL can be enrolled if LMW heparin can be safely discontinued at least 24 hours prior to invasive vascular procedures (angiography and SIR-sphere administration)
  • Adequate renal function: serum creatinine ≤ 1.5 x ULN
  • 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 childbearing potential must have a negative serum pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study.
  • Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information.

Who cannot join

  • Evidence of ascites, cirrhosis, portal hypertension or portal vein thrombosis
  • Prior radiation to the upper abdomen
  • Contraindications to angiography
  • Patients with extensive tumor replacement of the liver defined as tumor volume > 50% of liver
  • Lung shunt ≥ 20%
  • Prior treatment with any investigational drug within the preceding 4 weeks
Show all 36Show fewer
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines.
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Symptomatic congestive heart failure of New York Heart Association Class III or IV
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
  • Severely impaired lung function as defined as spirometry and diffusing capacity of lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
  • Uncontrolled diabetes as defined by hemoglobin A1C (HbA1c) > 7% despite therapy.
  • Active (acute or chronic) or uncontrolled severe infections
  • Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C)
  • History of liver disease such as cirrhosis or chronic active hepatitis. Presence of Hepatitis B surface antigen (HepBSAg) or presence of hepatitis C antibody. History of, or current alcohol misuse/abuse within the past 12 months
  • Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot)
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients with an active, bleeding diathesis
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes. (Women of childbearing potential [WOCBP] must have a negative urine or serum pregnancy test within 14 days prior to administration of pasireotide and everolimus) Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
  • Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  • Patients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus).
  • Patients with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients
  • Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR formulations
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol
  • QT related exclusion criteria include:
  • QT Fridericia's Correction Formula (QTcF) at screening > 450 msec
  • History of syncope or family history of idiopathic sudden death
  • Sustained or clinically significant cardiac arrhythmias
  • Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular (AV) block
  • Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
  • Concomitant medication(s) known to increase the QT interval
  • Known gallbladder or bile duct disease, acute or chronic pancreatitis

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

Other trials in United States

About this study

Official title: Phase IB/II Study of Pasireotide, Everolimus and Selective Internal Radioembolization Therapy (SIRT) for Unresectable Neuroendocrine Hepatic Metastases

The purpose of this study is to see the safety and activity of using pasireotide, everolimus and radioembolization (Selective Internal Radioembolization Therapy-SIRT) in the treatment of neuroendocrine tumors (carcinoid) that has spread to the liver. Both everolimus or radioembolization are considered "standard of care" regimens in patients with liver lesions from neuroendocrine tumors. However, the use of the combination of everolimus and radioembolization has not been formally evaluated in the setting of a clinical trial. Pasireotide is a medication that is intended to block the hormonal secretions from the neuroendocrine tumors.

This study is divided into two parts. In the first part, the aim of the study is to determine the safety of combining everolimus, pasireotide, and radioembolization. For this part of the study the investigators will enroll up to 18 patients. After the investigators confirm the safety of the combination, they will conduct the second part of the study which will focus on evaluating the effectiveness of the combination. For this part of the study the investigators intend to enroll a total of 37 patients.

Read the detailed description

Liver metastasis remain a major challenge in the care of patients with Neuroendocrine Tumors (NET). This study is evaluating the combination of systemic therapies plus radioembolization for the treatment of liver metastasis from NET. The study allows pancreatic and intestinal NET that have spread to the liver.

Being tested
Pasireotide, Sir-sphere Radioembolization, Everolimus
Keywords
Neuroendocrine hepatic tumors, Liver cancer, Metastatic liver cancer
Medical subject headings
Neuroendocrine Tumors, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PasireotideDrug

    Also called SOM230, Signifor

    Pasireotide is given as an injection.

  • Sir-sphere RadioembolizationProcedure or surgery

    Also called Selective Internal Radioembolization Therapy, SIRT

    A catheter will be placed in a branch of the hepatic artery (liver) that supplies the tumor with blood. Radioactive beads will be injected into the tumor through the catheter.

  • EverolimusDrug

    Also called RAD001, Afinitor

    Given orally every day for the duration of the study

Study groups in NCT01469572
Study groupRoleWhat they receive
Sir-sphere radioembolizationExperimentalEverolimus, Pasireotide and Sir-sphere radioembolization
Receives: Drug: Pasireotide; Procedure: Sir-sphere Radioembolization; Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluate the number of patients who develop side effects from combination therapy.

    Determine the maximum tolerated dose of pasireotide and everolimus that can be administered with SIR spheres. Patients will be treated in cohorts of three. Dose of everolimus will be increased after every three patients. Plan is to determine the maximum dose that can be administered with less than 2 out of 6 patients develop significant side effects.

    Measured: 1 month

Secondary outcomes (1)

  1. Compare the size of the tumor before and three months after treatment using cross sectional imaging (CT ro MRI)

    To evaluate the response rate associated with the combination of pasireotide, everolimus and radioembolization. Response is defined as radiologic shrinkage in the size of the tumor.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionOct 2018
  4. Study completionOct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01469572
Sponsor's protocol ID
IRB00051599
Other IDs
WCI2031-11
Status last verified
Oct 2018
First submitted
13 Oct 2011
Last updated
18 Oct 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Kim HS, Shaib WL, Zhang C, Nagaraju GP, Wu C, Alese OB, Chen Z, Brutcher E, Renfroe M, El-Rayes BF. Phase 1b study of pasireotide, everolimus, and selective internal radioembolization therapy for unresectable neuroendocrine tumors with hepatic metastases. Cancer. 2018 May 1;124(9):1992-2000. doi: 10.1002/cncr.31192. Epub 2018 Feb 16.

    PubMed 29451701

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pasireotide, Sir-sphere Radioembolization and Everolimus in people with Neuroendocrine Tumors, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the number of patients who develop side effects from combination therapy. (time frame: 1 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01469572, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in