An Open-Label, Phase II Study of Cabozantinib (XL184) in Advanced Pancreatic Neuroendocrine and Carcinoid Tumors
An Open-Label, Phase II Study of Cabozantinib (XL184) in Advanced Pancreatic Neuroendocrine and Carcinoid Tumors
Cabozantinib works by blocking the growth of new blood vessels that feed a tumor. In addition to blocking the formation of new blood cells in tumors, cabozantinib also blocks pathways that may be responsible for allowing cancers cells to become resistant to other "anti-angiogenic" drugs. Cabozantinib has been studied or is being study in research studies as a possible treatment for various types of cancer, including prostate cancer, brain cancer, thyroid cancer, lung cancer, and kidney cancer.
In this research study, the investigators wish to learn if cabozantinib is effective in treating patients with pancreatic neuroendocrine and carcinoid tumors.
Subjects will take cabozantinib orally, once per day, in cycles of 28 days.
During each cycle subjects will have the following procedures:
On Day 15 (beginning of week 3) during the first 3 cycles:
Inclusion Criteria:
Locally unresectable or metastatic, histologically-confirmed, carcinoid or pancreatic neuroendocrine tumor. Tumors must be considered well- or moderately-differentiated. Patients with poorly differentiated neuroendocrine carcinoma or cell carcinoma are excluded from the study.
A tumor sample is required for enrollment (except for patients diagnosed > 7 years ago).
Must have measurable disease by RECIST criteria
Must have evidence of progressive disease within 12 months of study entry
Prior or concurrent therapy with somatostatin analogs is permitted. If on somatostatin/octreotide, must be on a stable dose for at least two months.
Age ≥ 18 years
No major surgery or radiation in the prior 4 weeks prior to enrollment
No prior therapy with cabozantinib
ECOG Performance status ≤ 1
Participants must have adequate organ and marrow function as defined below:
Sexually active subjects must agree to use medically accepted methods of birth control during the course of the study and for 3 months following discontinuation of study treatments (excluding women who are not of child bearing potential and men who have been sterilized).
Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
Subjects receiving any other standard or investigational anticancer agents, with the exception of somatostatin/octreotide therapy. If patients has received prior cytotoxic chemotherapy, must be at least three weeks since last treatment before first dose of study treatment.
Major surgery or radiation treatment <4 weeks prior to enrollment. In addition, cannot have received radiation to the thorax or gastrointestinal tract within three months of the first dose of study treatment.
Cannot have received radionuclide treatment within 6 weeks of first dose of study treatment.
High grade or poorly differentiated neuroendocrine tumors
Ongoing immunosuppression with systemic steroids or other immune modulator
Presence of CNS metastatic disease
Uncontrolled hypertension defined by SBP > 140 or DBP > 90 despite titration of anti hypertensive medications
No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia other than chronic atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements. Congestive heart failure or symptomatic coronary artery disease within 3 months prior to enrollment
Cerebrovascular accident within prior 6 months
The subject has a history of clinically significant hematemesis or a recent history of hemoptysis of > 2.5 mL of red blood or other signs indicative of pulmonary hemorrhage or evidence of endobronchial lesion(s).
The subject has a pulmonary lesion abutting or encasing a major blood vessel.
Previous history of pulmonary embolism or deep venous thrombosis
The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents (eg, clopidogrel). Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic Low Molecular Weight Heparin (LMWH) are permitted.
At the time of screening, active peptic ulcer disease or active inflammatory bowel disease (including ulcerative colitis or Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis, or appendicitis.
History of abdominal fistula, gastrointestinal perforation, bowel obstruction, gastric outlet obstruction, or intra-abdominal abscess within six months of study enrollment.
History of GI surgery within the past 28 days. If >28 days since GI surgery, must have confirmation of complete healing before initiating treatment with study drug.
Other disorders associated with a high risk of fistula formation, including PEG tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea or esophagus.
Other clinically significant disorders such as:
The subject has a corrected QT interval calculated by the Fridericia formula > 500ms within 28 days before randomization.
Severely impaired lung function
Concurrent malignancy (other than non-melanoma skin cancer) diagnosed within the past 3 years or any currently active malignancy
Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with the treatment protocol, breastfeeding should be discontinued if the mother is treated on protocol.