JCOG1901: An intergroup phase III study of combination therapy with everolimus and lanreotide versus everolimus monotherapy for unresectable or recurrent gastroenteropancreatic neuroendocrine tumor

JRCT ID: jRCT1031200023

Registered date:27/04/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Unresectable or reccurent gastroenteropancreatic neuroendocrine tumor.
• Date of first enrollment: 18/05/2020
• Target sample size: 250
• Study type: Interventional

Intervention(s)

Arm A : Daily oral administration of everolimus (10mg/body), until meeting the termination criteria for protocol treatment.
Arm B : Daily oral administration of everolimus (10mg/body) and deep subcutaneous injection of lanreotide (120mg/body) every 28 days, until meeting the termination criteria for protocol treatment.

Outcome(s)

• Primary Outcome: progression free survival
• Secondary Outcome: Overall survival (key secondary), response rate, disease control rate, adverse event rate.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Histologically proven well-differentiated neuroendocrine tumor.
(2) HE-stained section and immunostained sections for Chromogranin A, Synaptophysin, and Ki-67 of the biopsy specimen, used for diagnosis in (1) is available for central pathological review.
(3) Primary tumor is located in the pancreas, duodenum (excluding the ampulla of Vater), jejunum, ileum, stomach, colon, or rectum.
(4) Unresectable primary tumor or unresectable recurrent tumor. In cases of recurrent tumors diagnosed in imaging studies, histologic reconfirmation of the recurrent location or the primary location in not mandatory if the diagnosis of the primary location is confirmed in the past.
(5) Non-functional neuroendocrine tumor.
(6) Satisfies either (i) or (ii).
(i) Ki-67 LI >= 5% and Ki-67 LI <= 20%
(ii) Ki-67 LI < 5% and diffuse bilobar liver metastases
(7) Mitotic count <= 20 /10HPF if mitotic count is obtained.
(8) Aged 20 years and older at the time of enrollment.
(9) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
(10) Measurable region is not required.
(11) No history of systemic pharmacotherapy to NETs. Local treatments such as TACE(transcatheter arterial chemoembolization), TAE(transarterial embolization), RFA(radiofrequency ablation) are permissible.
(12) Adequate oral intake.
(13) Sufficient organ function. (Test results must be obtained within 14 days before enrollment.)
(i) Neutrophil count >= 1,200/mm3
(ii) Hemoglobin >= 8.0 g/dL(transfusion within 14 days before the blood test is not permissible)
(iii) Platelet count >= 75000 /mm3
(iv) Total bilirubin <= 2.0 mg/dL
(v) AST <= 100 U/L(<= 200 U/L if liver metastasis present)
(vi) ALT <= 100 U/L(<= 200 U/L if liver metastasis present)
(vii) Creatinine <= 1.5 mg/dL
(viii) Casual blood glucose <= 200 mg/dL
(14) Written informed consent.

Exclude criteria

(1) History of synchronous or metachronous (within 2 years) malignancies with 5-year relative survivals of less than 95% at the time of diagnosis.)
(2) Active infection requiring systemic therapy other than viral hepatitis.
(3) Fever of higher than 38.0 degrees celsius at the time of enrollment.
(4) Pregnant, possibly pregnant, within 28 days after delivery, breastfeeding female or males expecting conception of their child.
(5) Psychiatric illnesses or symptoms affecting daily lives.
(6) Systemic administration of steroids or immunosuppressive agents.
(7) Interstitial pneumonia, pulmonary fibrosis, or severe emphysema on chest CT.
(8) Severe complications such as heart failure, renal failure, liver failure, hemorrhagic gastric ulcer, intestinal paralysis, or bowel obstruction.
(9) Unstable angina (diagnosis or worsening of chest pain within 6 weeks) or history of myocardial infarction within 6 months prior to enrollment.
(10) Uncontrollable diabetes (HbA1c > 8%).
(11) Positive for HIV antibodies.
(12) Administration of live attenuated vaccines within 7 days of enrollment.

Related Information

• Primary Sponsor: MIZUNO Nobumasa
• Secondary Sponsor: Boku Narikazu
• Source(s) of Monetary Support: National Cancer Center Japan,Japan Agency for Medical Research and Development