Personalized CAPTEM Radiopeptide Therapy of Advanced, Non-resectable Neuroendocrine Cancer

NCT04194125 | Unknown Phase 2 DMC

• 1 other identifier: POLNETS_2018
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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 (CAP) and temozolomide (TEM) - 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.

Conditions

Neuroendocrine Tumors

Keywords

PRRT - Peptide Receptor Radionuclide Therapy; CAPTEM - Capecitabine-temozolomide; GET-NET - Gastro-Entero-Pancreatic Neuroendocrine Tumours; PFS - progression free survival; OS - overall survival

Outcome Measures

Primary Outcomes (1)

• PFS - Progression Free Survival

  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.

  3 years

Secondary Outcomes (10)

• OS - Overall Survival (time months)

  5 years

• Performance Status (PS) - evaluation criteria

  5 years

• Cancer Related Symptoms - assessment of clinical criteria

  5 years

• Hormonal overproduction symptoms - assessment of clinical criteria

  5 years

• ORR - Objective Response Rate - evaluation criteria

  5 years

Study Arms (1)

177Lu-DOTATOC combined with CAPTEM

EXPERIMENTAL

* The therapy will include 4 courses (14 days per one) with 8-week intervals; * 177Lu-DOTATOC in doses from 5,55GBq up to 7,4 GBq will be administered i.v. up to four times at 10th day; * Concomitant amino acids will be given with each administration; * Capecitabine will be administrated for 14 days (twice a day) followed by Temozolomide at 10-14th days in each therapy sessions.

Drug: 177Lu-DOTATOC

Interventions

177Lu-DOTATOC DRUG

Four administrations of 5,55GBq up to 7,4 GBq 177Lu-DOTATOC will be administered at 8-week intervals.

177Lu-DOTATOC combined with CAPTEM

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years old, male or female;
• All patients with histologically proven, well/moderate-differentiated G1/2 GEP-NET (according to WHO 2017 classification), with Ki-67 ≤20%, in selected cases patients with NETG3 will be included if there will be reported well/moderate morphological appearance but Ki-67\>20% but less then Ki\<30% (pancreatic, midgut NET and cancer with unknown primary (CUP)); and there will be high expression of somatostatin receptor seen in functional imaging utilized functional imaging 99mTc HYNICTOC or 68Ga DOTATATE or 68Ga DOTATOC;
• The presence of high expression of somatostatin receptors demonstrated on Somatostatin Receptor Imaging using 99mTc HYNICTOC (SPECT) or 68Ga DOTATATE or 68Ga DOTATOC (PET) scans, et least as uptake in not involved liver, Krenning \>2;
• Non-resectable, advanced determined by an appropriately specialized surgeon or deemed not suitable for liver directed therapies where liver is the only site of disease;
• Performance status (PS) based on ECOG 0-2;
• Unresectable, advanced/metastatic progressive disease evaluated as clinical, biochemical, bad control symptoms of tumour hypersecretion or disease progression seen in imaging structural or functional;
• Parameteres of laboratory test:
• Morphology: Hb\>10g/dl, PLT\>75x103/ml, WBC\> 2x103 /ml with ACN\> 1.5x103/ml
• Adequate renal function (GFR\>30 ml/min)\*, creatinine \<1.5 mg/dl
• Adequate liver function (Bilirubin \<1.8 mg/dl, ALAT and ASPAT, AP \<5 ULN (ULN - upper limit of normal) \* The patient may be qualificated to supportive treatment if the patient's condition is stable.
• Life expectancy of at least 6 months;
• The tumor parameters that can be measured objectively as the size to be assessed in radiological studies on the basis of the RECIST 1.0 and RECIST 1.1;
• In the absence of the ability to measure tumor size based on RECIST criteria, they have tumor parameters that can be measured objectively as tumor markers determined in the blood or urine CgA, 5HIAA;
• Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
• Signed, written informed consent.

You may not qualify if:

• Patients \<18 years old;
• Coexistence of another cancer during recent 5 years, except cancers treated with curative intention and confirmed cured in follow-up with no or low risk of relapse;
• Allergy on somatostatin receptor analogues or capecitabine and temozolomide;
• Previous cytotoxic chemotherapy e.g. CAPTEM, and/or radiopeptide therapy PRRT;
• Pre-existing locoregional treatment such as radiomebolization (SIRspheres) or HDR brachytherapy under CT control, performed in the last 6 months;
• Uncontrolled metastases to the central nervous system, in the case of surgical and/or radiotherapeutic treatment, patients should remain on a stable dose of steroids for at least 2 weeks before enrollment, without deterioration of the general state associated with the presence of metastatic disease in the CNS;
• Poorly controlled concurrent medical illness. E.g. unstable diabetes with glycosylated hemoglobin (HbA1c\> 9.0), the optimal glycaemic control should be achieved before starting trial therapy);
• Major surgery/surgical therapy for any cause within three months before starting trial therapy;
• Symptomatic heart failure NYHA class III or IV, congestive cardiac failure, myocardial infarction in the last 6 months, serious uncontrolled cardiac arrhythmia, unstable angina, or other serious cardiac problems;
• Patients with malabsorption or other gastrointestinal disorders that may interfere with the oral absorption of capecitabine and temozolomide (e.g. colitis ulcerosa, persistent nausea, vomiting, persistent diarrhea) not suitable for conservative treatment and no reaction to SST receptor analogs (Sandostatin LAR or Somatulina Autogel), malabsorption syndrome, short bowel syndrome after resection
• Active uncontrolled infection, including Hepatitis and Hepatitis, HIV, in the case of HCV and HBV infection, the patient can be included in the study confirming the suppression of viral replication and the patient remains on the correct therapeutic dose of antiviral drugs;
• Pregnant patients (a negative pregnancy test is required);
• Women of childbearing age must present a negative pregnancy test at the beginning of the study and must use double barrier to contraception. Women of childbearing age are defined as menopausal if they remain not menstrual for at least 1 year, or surgical sterilization or removal of the uterus before the start of the study;
• Breast-feeding female patients;
• Patients in a mental state who can't understand the nature, extent and possible consequences of participating in the study associated with radioisotope treatment, or there is evidence of a lack of cooperation by the patient;

Sponsors & Collaborators

• University of Warmia and Mazury: lead
• Maria Sklodowska-Curie National Research Institute of Oncology: collaborator
• Medical University of Warsaw: collaborator
• The Diagnostic and Therapeutic Center Gammed; Poland: collaborator
• National Center for Research and Development, Poland: collaborator

Study Sites (1)

Centrum Diagnostyczno-Lecznicze Gammed

Warsaw, 02-351, Poland

RECRUITING

Related Publications (14)

• 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

• Fine RL, Gulati AP, Krantz BA, Moss RA, Schreibman S, Tsushima DA, Mowatt KB, Dinnen RD, Mao Y, Stevens PD, Schrope B, Allendorf J, Lee JA, Sherman WH, Chabot JA. Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience. Cancer Chemother Pharmacol. 2013 Mar;71(3):663-70. doi: 10.1007/s00280-012-2055-z. Epub 2013 Jan 31.

  PMID: 23370660 BACKGROUND

• Saif MW, Kaley K, Brennan M, Garcon MC, Rodriguez G, Rodriguez T. A retrospective study of capecitabine/temozolomide (CAPTEM) regimen in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs) after failing previous therapy. JOP. 2013 Sep 10;14(5):498-501. doi: 10.6092/1590-8577/1589.

  PMID: 24018594 BACKGROUND

• Peixoto RD, Noonan KL, Pavlovich P, Kennecke HF, Lim HJ. Outcomes of patients treated with capecitabine and temozolamide for advanced pancreatic neuroendocrine tumors (PNETs) and non-PNETs. J Gastrointest Oncol. 2014 Aug;5(4):247-52. doi: 10.3978/j.issn.2078-6891.2014.019.

  PMID: 25083296 BACKGROUND

• Koumarianou A, Kaltsas G, Kulke MH, Oberg K, Strosberg JR, Spada F, Galdy S, Barberis M, Fumagalli C, Berruti A, Fazio N. Temozolomide in Advanced Neuroendocrine Neoplasms: Pharmacological and Clinical Aspects. Neuroendocrinology. 2015;101(4):274-88. doi: 10.1159/000430816. Epub 2015 Apr 29.

  PMID: 25924937 BACKGROUND

• De Divitiis C, von Arx C, Grimaldi AM, Cicala D, Tatangelo F, Arcella A, Romano GM, Simeone E, Iaffaioli RV, Ascierto PA, Tafuto S; European Neuroendocrine Tumor Society (ENETS) Center of Excellence-Multidisciplinary Group for Neuroendocrine Tumors in Naples (Italy). Metronomic temozolomide as second line treatment for metastatic poorly differentiated pancreatic neuroendocrine carcinoma. J Transl Med. 2016 May 3;14(1):113. doi: 10.1186/s12967-016-0857-1.

  PMID: 27142424 BACKGROUND

• Ramirez RA, Beyer DT, Chauhan A, Boudreaux JP, Wang YZ, Woltering EA. The Role of Capecitabine/Temozolomide in Metastatic Neuroendocrine Tumors. Oncologist. 2016 Jun;21(6):671-5. doi: 10.1634/theoncologist.2015-0470. Epub 2016 May 25.

  PMID: 27226359 BACKGROUND

• Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, Feelders RA, van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008 May 1;26(13):2124-30. doi: 10.1200/JCO.2007.15.2553.

  PMID: 18445841 BACKGROUND

• Cwikla JB, Sankowski A, Seklecka N, Buscombe JR, Nasierowska-Guttmejer A, Jeziorski KG, Mikolajczak R, Pawlak D, Stepien K, Walecki J. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010 Apr;21(4):787-794. doi: 10.1093/annonc/mdp372. Epub 2009 Oct 15.

  PMID: 19833821 BACKGROUND

• Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, Bartolomei M, Lombardo D, Ferrari ME, Sansovini M, Chinol M, Paganelli G. Peptide receptor radionuclide therapy with (1)(7)(7)Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging. 2011 Dec;38(12):2125-35. doi: 10.1007/s00259-011-1902-1. Epub 2011 Sep 3.

  PMID: 21892623 BACKGROUND

• Hicks RJ, Kwekkeboom DJ, Krenning E, Bodei L, Grozinsky-Glasberg S, Arnold R, Borbath I, Cwikla J, Toumpanakis C, Kaltsas G, Davies P, Horsch D, Tiensuu Janson E, Ramage J; Antibes Consensus Conference participants. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasia: Peptide Receptor Radionuclide Therapy with Radiolabeled Somatostatin Analogues. Neuroendocrinology. 2017;105(3):295-309. doi: 10.1159/000475526. Epub 2017 Apr 13. No abstract available.

  PMID: 28402980 BACKGROUND

• Claringbold PG, Turner JH. Pancreatic Neuroendocrine Tumor Control: Durable Objective Response to Combination 177Lu-Octreotate-Capecitabine-Temozolomide Radiopeptide Chemotherapy. Neuroendocrinology. 2016;103(5):432-9. doi: 10.1159/000434723. Epub 2015 Jun 10.

  PMID: 26065489 BACKGROUND

• Claringbold PG, Brayshaw PA, Price RA, Turner JH. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011 Feb;38(2):302-11. doi: 10.1007/s00259-010-1631-x. Epub 2010 Oct 30.

  PMID: 21052661 BACKGROUND

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

177Lu-octreotide, DOTA(0)-Tyr(3)-

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Central Study Contacts

Jarosław B Ćwikła, MD, PhD

CONTACT

+48602112599; jbcwikla@interia.pl

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: Head of Department of Nuclear Medicine

Study Record Dates

• First Submitted: December 7, 2019
• First Posted: December 11, 2019
• Study Start: February 1, 2019
• Primary Completion: June 30, 2021
• Study Completion: January 31, 2022
• Last Updated: November 4, 2020

Record last verified: 2020-11

Locations

PL (1)