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

NCT03079440 | Completed Phase 2

• 1 other identifier: Asan-ONCHBP-2017-002
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neuroendocrine Tumors; Neuroendocrine Carcinoma; Temozolomide; Capecitabine

Keywords

Neuroendocrine tumors; Neuroendocrine Carcinoma; Capecitabine; Temozolomide

Outcome Measures

Primary Outcomes (1)

• Response rate

  Proportion of patients with complete or partial response graded by Response Evaluation Criteria in Solid Tumors version 1.1

  2 years

Secondary Outcomes (3)

• Progression-free survival

  2 years

• Overall survival

  2 years

• Toxicity (Adverse events graded by National Cancer Institute-Common Terminology Criteria version 4.03)

  2 years

Study Arms (1)

TEMCAP

EXPERIMENTAL

Temozolomide plus Capecitabine

Drug: TEMCAP

Interventions

TEMCAP DRUG

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

Also known as: Temozolomide and capecitabine

TEMCAP

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center, University of Ulsan College of Medicine

Seoul, 05505, South Korea

Location

Related 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.

  PMID: 26731334 BACKGROUND

• 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.

  PMID: 24771552 BACKGROUND

• 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.

  PMID: 22967994 BACKGROUND

• 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.

  PMID: 20824724 BACKGROUND

• 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.

  PMID: 21456005 BACKGROUND

MeSH Terms

Conditions

Neuroendocrine Tumors; Carcinoma, Neuroendocrine

Interventions

Temozolomide; Capecitabine

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Baek-Yeol Ryoo, MD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 14, 2017
• Study Start: May 15, 2017
• Primary Completion: November 15, 2020
• Study Completion: November 15, 2022
• Last Updated: December 6, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)