Overview

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

Status:
Unknown status
Trial end date:
2020-12-01
Target enrollment:
0
Participant gender:
All
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).
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Australasian Gastro-Intestinal Trials Group
Treatments:
Capecitabine
Dacarbazine
Temozolomide
Criteria
Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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 .