TEMCAP in Grade 3 and Low Ki-67 Gastroenteropancreatic Neuroendocrine Tumors

Neuroendocrine Tumors Clinical Trial

Official title:

Phase 2 Study of Temozolomide Plus Capecitabine in Patients With Grade 3 and Low Ki-67 Gastroenteropancreatic Neuroendocrine Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03079440
• Other study ID #: Asan-ONCHBP-2017-002
• Status: Completed
• Phase: Phase 2
• Start date: May 15, 2017
• Est. completion date: November 15, 2022

Study information

• Verified date: December 2022
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GI tract including pancreas is the one of most common primary sites of neuroendocrine tumors. Current grading of neuroendocrine tumors are based on the 2010 WHO classification. This classifies grade 3 tumors as the neuroendocrine tumor with mitosis > 20 per 10 high power field or Ki-67 labeling index > 20%. Etoposide-based chemotherapy, mostly as the combination with cisplatin, has been the mainstay of the treatment for patients with grade 3 neuroendocrine tumors. However, a recent large retrospective analysis has suggested this regimen may not be effective in relatively low Ki-67 labeling index. Therefore, the investigators designed a clinical trial testing temozolomide-capecitabine combination, which has been mostly investigated in well differentiated (ie., grade 1 or 2) neuroendocrine tumors, in patients with grade 3 and low Ki-67 gastroenteropancreatic neuroendocrine tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: November 15, 2022
• Est. primary completion date: November 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Patients aged 19 years and older

• Histologically confirmed neuroendocrine tumors of gastrointestinal tract or pancreas

• Unresectable or metastatic disease

• Grade 3 according to the 2010 WHO classification (Ki-67 labeling index > 20% or > 20 mitoses per 10 high power field)

• Ki-67 labeling index < 60%

• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1

• Eastern Cooperative Oncology Group (ECOG) performance status 0 ~ 2

• Adequate bone marrow function as defined by platelets = 100 x 109/L and neutrophils = 1.5 x 109/L

• Adequate renal function, with serum creatinine < 1.5 x upper limit of normal (ULN)

• Adequate hepatic function with serum total bilirubin < 2 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN

• No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other non life-threatening cancer (i.e., prostate or thyroid cancer) except where treated with curative intent > 5 years previously without evidence of relapse

• Written informed consent to the study

Exclusion Criteria:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance

• Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy

• Obstruction of gastrointestinal tract

• Active gastrointestinal bleeding

• Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)

• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol

• Female subjects who are pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug. A highly effective method of contraception is defined as having a low failure rate (< 1% per year) when used consistently and correctly.

Related Conditions & MeSH terms

• Capecitabine
• Carcinoma, Neuroendocrine
• Neuroendocrine Carcinoma
• Neuroendocrine Tumors
• Temozolomide

Intervention

Drug:
• TEMCAP
Oral capecitabine 750 mg/m2 twice a day, Day 1 to 14 and oral temozolomide 200 mg/m2 once a day, Day 10 to 14

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center, University of Ulsan College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (5)

Garcia-Carbonero R, Sorbye H, Baudin E, Raymond E, Wiedenmann B, Niederle B, Sedlackova E, Toumpanakis C, Anlauf M, Cwikla JB, Caplin M, O'Toole D, Perren A; Vienna Consensus Conference participants. ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas. Neuroendocrinology. 2016;103(2):186-94. doi: 10.1159/000443172. Epub 2016 Jan 5. No abstract available. — View Citation

Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer. 2014 Sep 15;120(18):2814-23. doi: 10.1002/cncr.28721. Epub 2014 Apr 25. — View Citation

Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, Dueland S, Hofsli E, Guren MG, Ohrling K, Birkemeyer E, Thiis-Evensen E, Biagini M, Gronbaek H, Soveri LM, Olsen IH, Federspiel B, Assmus J, Janson ET, Knigge U. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013 Jan;24(1):152-60. doi: 10.1093/annonc/mds276. Epub 2012 Sep 11. — View Citation

Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT, Helm J, Kvols L. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011 Jan 15;117(2):268-75. doi: 10.1002/cncr.25425. Epub 2010 Sep 7. — View Citation

Welin S, Sorbye H, Sebjornsen S, Knappskog S, Busch C, Oberg K. Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy. Cancer. 2011 Oct 15;117(20):4617-22. doi: 10.1002/cncr.26124. Epub 2011 Mar 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	Proportion of patients with complete or partial response graded by Response Evaluation Criteria in Solid Tumors version 1.1	2 years
Secondary	Progression-free survival	Time between the start of study treatment and disease progression	2 years
Secondary	Overall survival	Time between the start of study treatment and survival	2 years
Secondary	Toxicity (Adverse events graded by National Cancer Institute-Common Terminology Criteria version 4.03)	Adverse events graded by National Cancer Institute-Common Terminology Criteria version 4.03	2 years