GastrinomaPhase 2NCT02031536
Everolimus in Patients With Pancreatic Neuroendocrine Tumors Metastatic to the Liver Previously Treated With Surgery
A Phase 2 study testing everolimus in people with Gastrinoma and Glucagonoma, run by ECOG-ACRIN Cancer Research Group at 1 site in United States.
Trial summary
This randomized phase II trial studies how well everolimus works in treating patients with pancreatic neuroendocrine tumors metastatic to the liver previously treated with surgery. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrinoma, Glucagonoma, Insulinoma
- What is being tested?
- everolimus
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2014to 19 Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients must have histologically or pathologically confirmed metastatic low or intermediate grade pancreatic neuroendocrine tumor(s) to the liver as per the Klimstra guidelines
- Patients must have recovered from an R0 or R1 resection of all disease (including resection of a primary primitive neuroectodermal tumor [PNET] if present); patients may have had resection plus microwave or radiofrequency ablation, provided that no ablated lesion was >= 5 cm prior to ablation
- Patients must be within 4 to 8 weeks from the completion of surgery at time of randomization
- Patients must have paraffin-embedded fixed metastatic tumor tissue available for submission for central review; core biopsy or surgical specimens required
- Patients must have post-operative computed tomography (CT) or magnetic resonance imaging (MRI) prior to randomization and =< 4 weeks after completion of surgery to confirm disease status; patients must be able to tolerate CT or MRI imaging including contrast agents as required for the protocol
- Women of child-bearing potential and sexually active males must be strongly advised to use an accepted and highly effective method of contraception or abstain from sexual intercourse for the duration of their treatment through 8 weeks after their last dose of protocol therapy; women of child-bearing potential, sexually active males, and the female partners of male participants should be advised of the risk of becoming pregnant or fathering a child while receiving protocol treatment; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
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- Prior treatment with sunitinib and/or cytotoxic chemotherapy are allowed provided last dose was > 30 days prior to randomization
- Prior chemoembolization is allowed provided last dose was > 30 days prior to randomization
- Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X institutional ULN
- Serum creatinine =< 1.5 X institutional ULN or creatinine clearance >= 60 mL/min for patients with creatinine levels above 1.5 X institutional normal
- Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN
- Absolute neutrophil count >= 1,500/mm^3
- Leukocytes >= 3,000/mm^3
- Platelets >= 100,000/mm^3
- Hemoglobin >= 9 g/dL
- Patients with a history of the following within =< 12 months of randomization are not eligible
- Arterial thromboembolic events
- Unstable angina
- Myocardial infarction
- Patients with known history of abnormal pulmonary function must have documentation of diffusing capacity of the lung for carbon monoxide (DLCO) of > 50% predicted and oxygen saturation (SaO2) of > 87% at rest on room air =< 4 weeks prior to randomization
- Patients with unexplained pulmonary infiltrates must have pulmonary function tests within the institutional limits of normal =< 4 weeks prior to randomization
- Patients with poorly controlled diabetes mellitus as defined by hemoglobin A1c (HbA1c) > 8% despite adequate therapy are ineligible; patients with a known history of impaired fasting glucose or diabetes mellitus must have blood glucose and antidiabetic treatment monitored closely throughout the trial and adjusted as necessary
- Patients may not be receiving any other investigational agents while on study treatment; prior treatment with other investigational agent is allowed provided last dose was >= 30 days prior to randomization
- Patients must NOT have received live attenuated vaccines =< 1 week prior to randomization; patients should also be advised not to receive live attenuated vaccines during the study and to avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Patients must have life expectancy >= 12 weeks
- Patients should be advised to avoid drugs or foods that are known potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or inducers
Who cannot join
- Patients have received prior everolimus
- Patients have either clinically apparent central nervous system metastases or carcinomatous meningitis =< 6 months prior to randomization
- Women are pregnant or breast-feeding; all females of childbearing potential must have a blood test within 2 weeks prior to randomization to rule out pregnancy
- Patients are on chronic treatment with corticosteroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed
- Patients have history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus
- Patients have known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
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- Patients have absorption issues that would limit the ability to absorb everolimus
- Patients have a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
- Patients have previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions:
- Non-melanoma skin cancer, in situ cervical cancer, breast cancer in situ, or superficial bladder cancer (noninvasive papillary carcinoma or carcinoma in situ); OR
- Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years
- Patients have severe and/or uncontrolled medical conditions such as:
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to randomization, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
- Symptomatic congestive heart failure of New York Heart Association class III or IV
- Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA])
- Active, bleeding diathesis
- Patients have known history of human immunodeficiency virus (HIV) seropositivity
- Patients have experienced thrombotic events (deep vein thrombosis, pulmonary embolism) =< 3 months prior to randomization
- Patients have liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis at randomization; patients at increased risk for hepatitis B or hepatitis C must be screened for hepatitis prior to randomization
- Patients have ongoing cardiac dysrhythmia of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0) grade >= 2, uncontrolled atrial fibrillation of any grade, or corrected QT (QTc) interval > 470 msec
- Patients have history of severely impaired pulmonary function for their age
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver
This randomized phase II trial studies how well everolimus works in treating patients with pancreatic neuroendocrine tumors metastatic to the liver previously treated with surgery. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus after surgery may kill any tumors cells that remain.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate if the addition of adjuvant everolimus to the R0 or R1 surgical resection of pancreatic neuroendocrine tumor metastases to the liver will result in an improvement in disease free survival.
SECONDARY OBJECTIVES:
- To evaluate if the addition of adjuvant everolimus to the R0 or R1 surgical resection of pancreatic neuroendocrine tumor metastases to the liver will result in an improvement in overall survival.
II. To evaluate the toxicity associated with adjuvant everolimus following resection in patients with metastatic pancreatic neuroendocrine tumors to the liver.
OUTLINE: Patients are randomized to 1 of 2 treatment arms in a 1:1 ratio.
ARM A: Patients receive everolimus orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: 150 patients
- Conditions
- Gastrinoma, Glucagonoma, Insulinoma, Liver Metastases, Pancreatic Polypeptide Tumor, Recurrent Islet Cell Carcinoma
- Being tested
- everolimus, placebo
- Keywords
- everolimus, randomized, metastatic pancreatic neuroendocrine tumors, liver
- Medical subject headings
- Gastrinoma, Glucagonoma, Insulinoma, Carcinoma, Islet Cell, Somatostatinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001
Given PO
placeboOther
Also called PLCB
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm A (everolimus) | Experimental | Patients receive everolimus PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: everolimus |
| Arm B (placebo) | Placebo comparator | Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Free Survival (DFS)
DFS is defined as time from randomization to disease recurrence or death, whichever occurred first. Patients who are still alive are censored at the last date of known free of recurrence.
Measured: assessed every 12 weeks while on treatment and then every 3 months if < 2 years from study entry; every 6 months up to 5 years from study entry or recurrence, whichever occurred first
Secondary outcomes (1)
Overall Survival (OS)
OS is defined as time from randomization to death from any cause. Patients who are still alive are censored at the last date of known alive.
Measured: assessed every 3 months if < 2 years from study entry, and every 6 months up to 5 years from study entry or death, whichever occurred first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2014 (estimated)
- Study start10 Apr 2014
- Primary completion19 Jul 2017
- Study completion19 Jul 2017
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GastrinomaStudies of the same condition, open and under way.
- More trials run by ECOG-ACRIN Cancer Research GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- ECOG-ACRIN Cancer Research Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Steven Libutti, Principal investigator, Eastern Cooperative Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02031536
- Sponsor's protocol ID
- E2212
- Other IDs
- NCI-2013-02484, ECOG-E2212, U10CA021115
- Status last verified
- Jun 2023
- First submitted
- 7 Jan 2014
- Last updated
- 29 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded, Placebo-Controlled Phase II Study of Adjuvant Everolimus Following the Resection of Metastatic Pancreatic Neuroendocrine Tumors to the Liver
- ClinicalTrials.gov ID
- NCT02031536
- Acronym / sponsor ID
- E2212
- Conditions
- Gastrinoma, Glucagonoma, Insulinoma, Liver Metastases, Pancreatic Polypeptide Tumor, Recurrent Islet Cell Carcinoma
- Keywords
- everolimus, randomized, metastatic pancreatic neuroendocrine tumors, liver
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- ECOG-ACRIN Cancer Research GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Apr 2014 (actual)
- Primary completion
- 19 Jul 2017 (actual)
- Study completion
- 19 Jul 2017 (actual)
- First posted
- 9 Jan 2014 (estimated)
- Results
- Posted 2 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial studies how well everolimus works in treating patients with pancreatic neuroendocrine tumors metastatic to the liver previously treated with surgery. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus after surgery may kill any tumors cells that remain.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate if the addition of adjuvant everolimus to the R0 or R1 surgical resection of pancreatic neuroendocrine tumor metastases to the liver will result in an improvement in disease free survival.
SECONDARY OBJECTIVES:
- To evaluate if the addition of adjuvant everolimus to the R0 or R1 surgical resection of pancreatic neuroendocrine tumor metastases to the liver will result in an improvement in overall survival.
II. To evaluate the toxicity associated with adjuvant everolimus following resection in patients with metastatic pancreatic neuroendocrine tumors to the liver.
OUTLINE: Patients are randomized to 1 of 2 treatment arms in a 1:1 ratio.
ARM A: Patients receive everolimus orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: 150 patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (everolimus) | Experimental | Drug: everolimusPatients receive everolimus PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
| Arm B (placebo) | Placebo comparator | Other: placeboPatients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Patients must have histologically or pathologically confirmed metastatic low or intermediate grade pancreatic neuroendocrine tumor(s) to the liver as per the Klimstra guidelines
- Patients must have recovered from an R0 or R1 resection of all disease (including resection of a primary primitive neuroectodermal tumor [PNET] if present); patients may have had resection plus microwave or radiofrequency ablation, provided that no ablated lesion was >= 5 cm prior to ablation
- Patients must be within 4 to 8 weeks from the completion of surgery at time of randomization
- Patients must have paraffin-embedded fixed metastatic tumor tissue available for submission for central review; core biopsy or surgical specimens required
- Patients must have post-operative computed tomography (CT) or magnetic resonance imaging (MRI) prior to randomization and =< 4 weeks after completion of surgery to confirm disease status; patients must be able to tolerate CT or MRI imaging including contrast agents as required for the protocol
Key exclusion criteria (21 listed)
- Patients have received prior everolimus
- Patients have either clinically apparent central nervous system metastases or carcinomatous meningitis =< 6 months prior to randomization
- Women are pregnant or breast-feeding; all females of childbearing potential must have a blood test within 2 weeks prior to randomization to rule out pregnancy
- Patients are on chronic treatment with corticosteroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed
- Patients have history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001Given PO | Drug | Arm A (everolimus) |
| placeboAlso: PLCBGiven PO | Other | Arm B (placebo) |
Primary outcome
Disease Free Survival (DFS)
Time frame: assessed every 12 weeks while on treatment and then every 3 months if < 2 years from study entry; every 6 months up to 5 years from study entry or recurrence, whichever occurred first
DFS is defined as time from randomization to disease recurrence or death, whichever occurred first. Patients who are still alive are censored at the last date of known free of recurrence.
1 secondary outcome
Overall Survival (OS)
Time frame: assessed every 3 months if < 2 years from study entry, and every 6 months up to 5 years from study entry or death, whichever occurred first
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Gastrinoma
Active, not recruitingObservational study
DOTATOC PET/CT for Imaging NET Patients
Neuroendocrine Tumors, Insulinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Libutti principal investigator
Eastern Cooperative Oncology Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus in people with Gastrinoma and Glucagonoma, run by ECOG-ACRIN Cancer Research Group 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 28 inclusion and 21 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: stopped early, as of the sponsor's last update on 29 Jun 2023. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Disease Free Survival (DFS) (time frame: assessed every 12 weeks while on treatment and then every 3 months if < 2 years from study entry; every 6 months up to 5 years from study entry or recurrence, whichever occurred first). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jun 2023.