Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study

NCT02358356 | Completed Phase 2 DMC

• 1 other identifier: CTC0120 / AG0114NET
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 4

Brief Summary

Two parallel phase II randomized open label trials of Lutetium-177 Octreotate (177Lu-Octreotate) peptide receptor radionuclide therapy (PRRT) and capecitabine (CAP)/temozolomide (TEM) chemotherapy (chemo): (i) versus CAPTEM alone in the treatment of low to intermediate grade pancreatic neuroendocrine tumours (pNETs); (ii) versus PRRT alone in the treatment of low to intermediate grade mid gut neuroendocrine tumours (mNETs).

Conditions

Midgut Neuroendocrine Tumours; Pancreatic Neuroendocrine Tumours

Keywords

midgut; pancreatic; neuroendocrine; advanced; unresectable low; intermediate grade; mNETs; pNETs

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  To determine the rate of progression free survival (PFS) at 12 months in pNETs (Group A), and at 24 months in mNETs (Group B). (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1).

  12 months for pNETs and 24 months for mNets

Secondary Outcomes (6)

• Objective tumour response rate (partial or complete response) as per RECIST v1.1 criteria

  12 months or 24 months as appropriate

• Overall survival (death from any cause)

  12 months or 24 months as appropriate

• Safety (rates of adverse events worst grade according to NCI CTCAE v4.0)

  12 months or 24 months as appropriate

• Quality of life (QOL scores determined at beginning, during treatment and until disease progression)

  12 months or 24 months as appropriate

• Resource utilisation (use of healthcare resources) and cost-effectiveness (Health utility score determined at beginning, during treatment and until end of follow up, correlated with MBS & PBS data)

  12 months or 24 months as appropriate

Other Outcomes (2)

• biomarkers CgA, Ki-67 and tumour MGMT expression with survival, response and safety.

  12 months or 24 months as appropriate

• Other measures of response such as 68Ga-DOTATATE, SUVmax, tumour update and other measures of response of a biochemical measure such as tumour markers, chomogranin A and patient reported outcomes.

  12 months or 24 months as appropriate

Study Arms (3)

PRRT

ACTIVE COMPARATOR

7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles.

Drug: octreotate

CAPTEM

ACTIVE COMPARATOR

Oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 every 28 day cycle, up to 8 cycles.

Drug: Capecitabine; Drug: Temozolomide

PRRT/CAPTEM

EXPERIMENTAL

7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 up to 4 cycles.

Drug: octreotate; Drug: Capecitabine; Drug: Temozolomide

Interventions

octreotate DRUG

7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV)

Also known as: lutate

PRRT; PRRT/CAPTEM

Capecitabine DRUG

oral capecitabine 750mg/m2 b.i.d.

Also known as: Xeloda

CAPTEM; PRRT/CAPTEM

Temozolomide DRUG

temozolomide 75mg/m2 b.i.d.

CAPTEM; PRRT/CAPTEM

Eligibility Criteria

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

You may qualify if:

• Adults ≥18 years old with histologically proven, moderate to well-differentiated G1/2 pancreatic or midgut NETs with Ki-67 \< 20%;
• The presence of somatostatin receptor avidity suitable for PRRT demonstrated on 68Ga-octreotate PET scan;
• Progressive advanced/metastatic disease that has progressed during or after ≤ 2 prior systemic therapies;
• Unresectable disease, determined by an appropriately specialized surgeon or deemed not suitable for liver directed therapies where liver is the only site of disease;
• ECOG performance status 0-2;
• Ability to swallow oral medication;
• Adequate renal function (measured creatinine clearance \> 50 ml/min by DTPA or 51CR-EDTA), bone marrow function (Hb \> 9 g/d/L, ANC \> 1.5 x109L, and platelets \> 100 x 10/L);
• Adequate liver function (serum total bilirubin ≤ 1.5 x ULN, and Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver metastases)). INR ≤ 1.5 (or on a stable dose of LMW heparin for \>2 weeks at time of enrolment .);
• Life expectancy of at least 9 months;
• Study treatment both planned and able to start within 28 days of randomisation; )
• 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:

• Primary NETs other than small bowel (midgut) or pancreatic NETs;
• Cytotoxic chemotherapy, targeted therapy, or biotherapy within the last four weeks;
• Prior intrahepatic 90Y microspheres, such as SIR-Spheres in the past six months;
• Prior Peptide Receptor Radionuclide Therapy;
• Major surgery/surgical therapy for any cause within one month;
• Surgical therapy of loco-regional metastases within the last three months prior to randomisation;
• Uncontrolled metastatic disease to the central nervous system. To be eligible, CNS metastases should have been treated with surgery and/or radiotherapy and the patient should have been receiving a stable dose of steroids for at least 2 weeks prior to randomisation, with no deterioration in neurological symptoms during this time;
• Poorly controlled concurrent medical illness. E.g. unstable diabetes (Note: optimal glycaemic control should be achieved before starting trial therapy); Symptomatic NYHA class III or IV congestive cardiac failure, myocardial infarction within 6 months of start of the study, serious uncontrolled cardiac arrhythmia, unstable angina, or any other clinically significant cardiac disease;
• History of other malignancies within 5 years except where treated with curative intent AND with no current evidence of disease AND considered not to be at risk of future recurrence Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible;
• Any uncontrolled known active infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated. Participants with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy;
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of capecitabine/temozolomide (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or substantial small bowel resection);
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
• Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception .

Sponsors & Collaborators

• Australasian Gastro-Intestinal Trials Group: lead

Study Sites (4)

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 8006, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

MeSH Terms

Conditions

Neuroectodermal Tumors, Primitive

Interventions

Capecitabine; Temozolomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nick Pavlakis, Associate Professor

  Royal North Shore Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: February 9, 2015
• Study Start: November 1, 2015
• Primary Completion: October 31, 2021
• Study Completion: October 31, 2021
• Last Updated: July 5, 2022

Record last verified: 2017-11

Locations

AU (4)