Personalized CAPTEM Radiopeptide Therapy of Advanced, Non-resectable Neuroendocrine Cancer
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|ClinicalTrials.gov Identifier: NCT04194125|
Recruitment Status : Recruiting
First Posted : December 11, 2019
Last Update Posted : December 11, 2019
This is a non-randomized, phase II, open label study. The purpose of this study is to estimate Progression Free Survival (PFS) after treatment with Peptide Receptor Radionuclide Therapy (PRRT) 177Lu-DOTATOC standard dose (up to 4x7,4GBq 177Lu DOTATOC) in combination with capecitabine (750mg/m2) and temozolomide (75mg/m2) (CAPTEM).
Patients with advanced, non-resectable and/or progressive gastro-entero-pancreatic neuroendocrine tumors, GEP-NET, (G1, G2), in selected cases with high proliferation index (Ki-67> 20%, usually below 55%), NETG3, with overexpression of somatostatin receptor (SSTR positive) will be enrolled in the study.
|Condition or disease||Intervention/treatment||Phase|
|Neuroendocrine Tumors||Drug: 177Lu-DOTATOC||Phase 2|
This is a non-randomized, phase II, open label study.
The purpose of this study is to:
• estimate Progression Free Survival (PFS) after treatment with Peptide Receptor Radionuclide Therapy (PRRT) 177Lu-DOTATOC standard dose (up to 4x7,4GBq 177Lu DOTATOC) in combination with capecitabine (750mg/m2) and temozolomide (75mg/m2) (CAPTEM).
Patients with advanced, non-resectable and/or progressive gastro-entero-pancreatic neuroendocrine tumors, GEP-NET according to WHO 2017 classification, (histological grade G1, G2), in selected cases patients with high proliferation index (Ki-67> 20%, usually below 55%), NETG3 - pancreatic, midgut neuroendocrine tumors and carcinoma of unknown primary (CUP). All with overexpression of somatostatin receptor (SSTR positive) based on somatostin receptor scintigraphy (SRS), will be enrolled in this study.
- evaluate the safety and tolerability of combination therapy using 177Lu-DOTATOC and CAPTEM.
- evaluate the health related quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-G.I.NET21 questionnaire.
- evaluate internal dosimetry, in a subset up to 20 patients, but at least 10 patients.
- explore the correlation of clinical efficacy outcomes with Somatostatin Receptor Scintigraphy (SRS) using 99mTc HYNICTOC (Tektordyt®) tumour uptake score.
- explore the correlation of clinical efficacy outcomes with the levels of some specific and non-specific biomarkers and gene transcripts analysis.
- compare the Time to Tumour Progression (TTP).
The schedule of treatment will include 4 courses; capecitabine (750mg/m2), which will be administrated for 14 days (twice a day) with 8-week breaks, combined at 10th day with 177Lu-DOTATOC (PRRT - Peptide Receptor Radionuclide Therapy) in doses from 5,55GBq up to 7,4 GBq administered i.v. up to four times in every patient.
In selected patients, in those with only liver involvement or dominant liver bulky disease third and fourth administration of PRRT will be used intraarterial administration (i.a.) via hepatic artery. The administered dose will be from 2.85 GBq up to 3.7GBq, up to two times per whole therapy, followed by Temozolomide p.o. administration (75mg/m2), which will be given during 10-14th days in each therapy sessions.
Doses of PRRT could be modified due to clinical stage and laboratory parameters. Treatment will be discontinued in the case of a cumulative dose 29,6 GBq, corresponding to the radiation dose on the bone marrow below 2 Gy and cumulative dose on kidney below 23 Gy. In case of radiation dose on kidney above 23 Gy treatment will be interrupted.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Clinical Study of Radiopeptide 177Lu-DOTATOC in Combination With Capecitabine and Temozolomide in Advanced, Non-resectable and Progressive Neuroendocrine Tumors With Somatostatin Receptor Overexpression|
|Actual Study Start Date :||February 1, 2019|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||January 31, 2022|
Experimental: 177Lu-DOTATOC combined with CAPTEM
Four administrations of 5,55GBq up to 7,4 GBq 177Lu-DOTATOC will be administered at 8-week intervals.
- PFS - Progression Free Survival [ Time Frame: 3 years ]
the time from the start of treatment date to the date of first observation of documented local recurrence, metastases or disease progression. Patients without progression at the time of analysis will be censored. The median PFS will be estimated.
Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
CT or MRI tumour assessment will be used to response evaluation. CT/MRI tumour assessment will be performed before start of PRRT and then after 6+2 weeks after last PRRT session followed by 6 months intervals during first 3 years of follow-up, after that annually. The measurement of PFS will be calculated in months.
- OS - Overall Survival (time months) [ Time Frame: 5 years ]Overall survival is defined as the time from the date of the start therapy to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off. The measurement of OS will be calculated in months.
- Performance Status (PS) - evaluation criteria [ Time Frame: 5 years ]Clinical response based on physical performance status (PS) using standard evaluation based on WHO/ECOG criteria. It will be assessed before each treatment cycle and then followed by 6 weeks after completion of therapy and then at three-month intervals. The measurement will be in the scale as follows: 0-asymptomatic, 1=symptomatic but completely ambulatory, 2=Symptomatic <50% in bed during the day, 3= Symptomatic >50% in bed during the day; 4=Bedbound; 5=Death.
- Cancer Related Symptoms - assessment of clinical criteria [ Time Frame: 5 years ]Clinical response based on potential relief in the initial phase before PRRT during and after PRRT. Items will be assessed, including: appetite, malaise, pain associated with the disease, nausea, vomiting, fever, wheezing and abdominal pain or any other symptoms of advanced cancer. All of the above will be assessed as yes / no. Intensity will be recorded in the quality assessment. It will be evaluated before treatment, before each treatment cycle, and then 6 weeks after the end of therapy, and then at three-month intervals. The measurement will be made in the qualitative data set and categorized as improvement, stabilization or disease progression.
- Hormonal overproduction symptoms - assessment of clinical criteria [ Time Frame: 5 years ]Hormonal response based on relief of symptoms of hormonal overproduction, which will be compare to clinical symptoms before PRRT, during and after PRRT during clinical follow-up. The presence of specific symptoms with hormone overproduction including: 1. Carcinoid syndrome (CS) - initial intensity of diarrhea and potential relief after PRRT (number per day), initial intensity of flushing and potential relief after PRRT (number per day). 2. Presence of heartburn in case of NET with ZES (Zollinger-Elisson syndrome) initial intensity and potential relief during PRRT and after finished PRRT during clinical follow-up. 3. Presence of hypoglycemia in case of NET with insulin overproduction (insulinoma), initial intensity of hypoglycemia before PRRT and potential relief after PRRT during clinical follow-up. The measurement will be made in a set of the qualitative data as improvement, stabilization or disease progression.
- ORR - Objective Response Rate - evaluation criteria [ Time Frame: 5 years ]The evaluation of objective response will be utilized by multiphase structural imaging before and after i.v. contrast enhancement (CT or MRI). The radiological response will be based on RECIST 1.0 using standard terminology of objective response, performed before start of PRRT and then after 6+2 weeks after last PRRT therapy followed by 6 months intervals during first 3 years of follow-up, after that annually. The measurement will be made in a set of quantitative data as partial response (PR), stable disease (SD) or disease progression (DP).
- Safety Assessments - Laboratory Parameters - evaluation criteria: CTCAEs ver. 4.0 [ Time Frame: 5 years ]Changes from Baseline in Hematology (WBC, RBC, platelets, haemoglobin), Blood chemistry (BUN, serum creatinine and creatinine clearance, uric acid, albumin, total bilirubin, AP, aspartate aminotransferase [AST/ASAT], alanine aminotransferase [ALT/ALAT], gamma-glutamyl transferase [γ-GT], [Na], [K], lactic dehydrogenase [LDH], glycosylated hemoglobin/hemoglobin A1c [glycoHb] and specific biomarkers Chromogranin-A (CgA) in the serum and 5-Hydroxyindoleacetic acid (5-HIAA) in the urine. The measurement will be made in a set of quantitative data, based on CTCAEs ver. 4.0. https://www.eortc.be/services/ doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf
- Vital Signs - heart rate - physiological parameter [ Time Frame: 5 years ]heart rate (beats per minute)
- Systolic and diastolic blood pressure - physiological parameter [ Time Frame: 5 years ]mmHg
- BMI - Body Mass Index - physiological parameter [ Time Frame: 5 years ]weight (kg), height (m) Body Mass Index (BMI kg/m2). The measurement will be made in a set of quantitative data
- ECG - physiological parameter [ Time Frame: 5 years ]ECG analysis during each therapy session and clinical follow-up, including: P Wave, QRS Complex, QT Interval. The measurement will be made in a set of quantitative data
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04194125
|Contact: Jarosław B Ćwikła, MD, PhDemail@example.com|
|Centrum Diagnostyczno-Lecznicze Gammed||Recruiting|
|Warszawa, Poland, 02-351|
|Contact: Jarosław B Ćwikła, M.D. +48602112599 firstname.lastname@example.org|
|Contact: Alina Czepukojć, M.Sc. +48228223001 ext Ćwikła email@example.com|
|Principal Investigator: Jarosław B Ćwikła, MD, PhD|
|Sub-Investigator: Nina Sekelcka|