Overview

Comparing Capecitabine and Temozolomide in Combination to Lutetium Lu 177 Dotatate in Patients With Advanced Pancreatic Neuroendocrine Tumors

Status:
Not yet recruiting
Trial end date:
2033-10-01
Target enrollment:
0
Participant gender:
All
Summary
This phase II trial compares capecitabine and temozolomide to lutetium Lu 177 dotatate for the treatment of pancreatic neuroendocrine tumors that have spread to other parts of the body (advanced) or are not able to be removed by surgery (unresectable). Chemotherapy drugs, such as capecitabine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and may reduce harm to normal cells. The purpose of this study is to find out whether capecitabine and temozolomide or lutetium Lu 177 dotatate may kill more tumor cells in patients with advanced pancreatic neuroendocrine tumors.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Alliance for Clinical Trials in Oncology
Collaborator:
National Cancer Institute (NCI)
Treatments:
Capecitabine
Lutetium Lu 177 dotatate
Temozolomide
Criteria
Inclusion Criteria:

- Histologic or pathologic documentation: well-differentiated pancreatic neuroendocrine
tumor (G1, G2, or well-differentiated G3) confirmed by local histology and/or
pathology

- Functional or nonfunctional tumors are allowed

- Stage: locally unresectable or metastatic disease

- Tumor Site: neuroendocrine tumor of pancreatic primary site

- Radiologic evaluation: tumor must have shown somatostatin receptor (SSTR) positivity
on 68Ga-DOTATATE PET or other SSTR-PET scan in the 12 months prior to registration;
however, documentation of SSTR positivity in the 6 months prior to registration is
preferred. SSTR positivity is defined as uptake greater than background liver in all
measurable lesions

- Patients are eligible if they meet one of the following criteria:

- Previously untreated patients with grade 2 or 3 disease AND with symptoms of
either disease bulk causing pain, anorexia, early satiety, large
effusions/ascites, abdominal pain, abdominal fullness due to hepatomegaly,
dyspnea) OR incompletely controlled symptoms of hormone excess despite
somatostatin analogue (SSA) and supportive care (including but not limited to:
diarrhea, hypercalcemia, hypoglycemia, hyperglycemia, flushing, Cushing's
syndrome). Patient may have been started on SSA for up to 2 months for attempted
symptom control without disease progression prior to registration

- Patients previously treated with SSA only and with disease progression by RECIST
in prior 12 months

- Patients previously treated with SSA and one or more prior systemic therapy must
have received prior anti-vascular endothelial growth factor (VEGF) pathway
therapy inhibitor OR have contraindication to anti-VEGF therapy (including but
not limited to: uncontrolled hypertension [systolic blood pressure [SBP] > 150
and/or diastolic blood pressure [DBP] > 90 despite medical management], stage IIB
or greater heart disease, angina pectoris, prior arterial [ATE] and venous
thromboembolic [VTE] events in the past 6 months, gastrointestinal [GI] bleed in
the last 6 months) and disease progression by RECIST in prior 12 months

- Patients previously treated with more than 2 lines of therapy, not including anti
VEGF therapy, but with NET related symptoms as outlined in first bullet (pain,
anorexia, early satiety, large effusions/ascites, abdominal pain, abdominal
fullness due to hepatomegaly, anorexia, early satiety, dyspnea) OR incompletely
controlled symptoms of hormone excess despite somatostatin analogue (SSA) and
supportive care (including but not limited to: diarrhea, hypercalcemia,
hypoglycemia, hyperglycemia, flushing, Cushing's syndrome).

- Any patient with disease progression by RECIST criteria in < 4 months

- Patients must have measurable disease per RECIST v1.1 by computer tomography (CT) scan
or magnetic imaging (MRI). Any lesions which have undergone percutaneous therapies or
radiotherapy after starting protocol therapy should not be considered measurable
unless the lesion has clearly progressed since the procedure.

* Lesions must be accurately measured in at least one dimension (longest diameter to
be recorded) as >= 1 cm with CT or MRI (or shortest diameter >= 1.5 cm for lymph
nodes). Non-measurable disease includes disease smaller than these dimensions or
lesions considered truly non- measurable including: leptomeningeal disease, bone
metastases, ascites, pleural or pericardial effusion, lymphangitic involvement of skin
or lung.

- Prior treatment with tyrosine kinase inhibitors (TKIs) such as mammalian target of
rapamycin (mTOR) inhibitors (e.g. everolimus, temsirolimus, etc.) or VEGF pathway
inhibitors (e.g. sunitinib, pazopanib, cabozantinib, bevacizumab, etc.) are allowed

- Prior treatment with hepatic intra-arterial embolic therapies is allowed if there is
recovery from all toxicities, measurable lesions do not include embolized liver unless
there has been clear subsequent progression, all measurable lesions are somatostatin
receptor avid, and treatment completed at least 2 months prior to registration

- Prior treatment with cryoablation or thermal/radiofrequency ablation of metastases is
allowed if there is recovery from all toxicities, measurable lesions do not include
treated metastases, and treatment completed at least 2 months prior to registration

- Age >= 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 9.0 g/dL

- Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine
clearance >= 30 mL/min (calculated by the Cockcroft-Gault equation)

- Total bilirubin =< 1.5 x ULN (in patients with liver metastases or known Gilbert's
syndrome, total bilirubin must be =< 3.0 x ULN)

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x
ULN

- Albumin >= 3.0 g/dL

- Concurrent somatostatin analog use while on protocol therapy is allowed provided that
the patient:

- Has a functional tumor (evidence of peptide hormones and/or bioactive substances
associated with a clinical hormone syndrome such as carcinoid syndrome or
Cushing's syndrome)

- Has been on a stable dose of somatostatin analog therapy for at least three
months

- Has previously demonstrated radiographic disease progression while on
somatostatin analog therapy. For subjects receiving lutetium Lu 177 dotatate,
there should be a minimum of 14 days between long-acting somatostatin analogue
and lutetium Lu 177 dotatate dosing. Short-acting somatostatin analogs should not
be administered within 24 hours of lutetium Lu 177 dotatate dosing. Following
lutetium Lu 177 dotatate dosing, long-acting somatostatin analogs may be
administered between 4 and 24 hours after each dose

Exclusion Criteria:

- Patients with poorly differentiated neuroendocrine carcinoma (large cell histology or
small cell histology) are not eligible

- No prior temozolomide, dacarbazine, capecitabine, 5-FU, or any PRRT for treatment of
the pNET

- Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic, and teratogenic effects

* Therefore, for women of childbearing potential only, a negative pregnancy test done
=< 14 days prior to registration is required

- No known brain metastases unless adequately treated, demonstrated to be stable, and
off all treatment (including steroids) for at least 2 months prior to registration

- No uncontrolled congestive heart failure (New York Heart Association [NYHA] II, III,
IV).

- No significant medical, psychiatric, or surgical condition, currently uncontrolled by
treatment, which may pose a risk to patient safety

- No "currently active" second malignancy other than non-melanoma skin cancers or
cervical carcinoma in situ. Patients are not considered to have a "currently active"
malignancy if they have completed therapy or are on adjuvant hormonal therapy and are
free of disease for >= 3 years

- No known medical condition causing an inability to swallow and no known impairment of
gastrointestinal function that may significantly alter the absorption of an oral agent