Everolimus in Patients With Pancreatic Neuroendocrine Tumors Metastatic to the Liver Previously Treated With Surgery

NCT02031536 | Terminated Phase 2 Results DMC

• 4 other identifiers: E2212NCI-2013-02484ECOG-E2212U10CA021115
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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. Giving everolimus after surgery may kill any tumors cells that remain.

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Liver Metastases; Pancreatic Polypeptide Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

Keywords

everolimus; randomized; metastatic pancreatic neuroendocrine tumors; liver

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  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

Study Arms (2)

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.

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.

Other: placebo

Interventions

everolimus DRUG

Given PO

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Arm A (everolimus)

placebo OTHER

Given PO

Also known as: PLCB

Arm B (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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 \[RNA\])

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ecog-Acrin

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Carcinoma, Islet Cell; Somatostatinoma

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenoma, Islet Cell; Adenoma; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Steven Libutti

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2014
• First Posted: January 9, 2014
• Study Start: April 10, 2014
• Primary Completion: July 19, 2017
• Study Completion: July 19, 2017
• Last Updated: June 29, 2023
• Results First Posted: December 2, 2020

Record last verified: 2023-06

Locations

US (1)