Cabozantinib in Advanced Pancreatic Neuroendocrine and Carcinoid Tumors

NCT01466036 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 11-274
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Carcinoid Tumor; Pancreatic Neuroendocrine Tumor

Keywords

metastatic

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The objective response rate of cabozantinib was evaluated according to RECIST v 1.1 criteria (Response Evaluation Criteria In Solid Tumors v 1.1). Disease was assessed using CT and/or MRI scans. RECIST 1.1 criteria include the following categories of disease response: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = 30% or more decrease in the sum of the longest diameter of target lesions; Stable disease (SD) = less than 30% decrease but no more than 20% increase in sum of the longest diameter of target lesions. Objective response rate consisted of CR + PR.

  Imaging was performed cycles 2,4,6 every 8 weeks for the first 24 weeks, then every 3rd cycle every 12 weeks until progression or EOT. Median treatment duration was 8 cycles for the Carcinoid cohort and 12.5 cycles for the PNET cohort. Cycle=28 days.

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  Restaging imaging was performed after cycles 2, 4, and 6 (every 8 weeks for the first 24 weeks), then every 3rd cycle (every 12 weeks) until disease progression or end of study treatment. Median follow-up is 89.1 months. Cycle = 28 days.

• Overall Survival (OS)

  Median follow-up time of 89.1 months.

Study Arms (2)

Metastatic or Unresectable PNET

EXPERIMENTAL

An anticipated 35 patients with pancreatic neuroendocrine tumors receiving cabozantinib

Drug: Cabozantinib

Metastatic or Unresectable Carcinoid

EXPERIMENTAL

An anticipated 35 patients with advanced or metastatic carcinoid tumor receiving cabozantinib

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

60 mg QD orally in cycles of 28 days

Also known as: XL184

Metastatic or Unresectable Carcinoid; Metastatic or Unresectable PNET

Eligibility Criteria

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

You may qualify if:

• 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:
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• Total bilirubin \</= 1.5X normal institutional limits
• AST (SGOT) and ALT (SGPT) \</=2.5x normal institutional limits, or \< 5x if liver metastases are present
• Creatinine \</= 1.5x normal institutional limits or creatinine clearance \> 50mL/min

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Carcinoid Tumor; Adenoma, Islet Cell; Neoplasm Metastasis

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Adenoma; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Jennifer Chan
• Organization: Dana-Farber Cancer Institute

jang@partners.org

617-632-6315

Study Officials

• Jennifer Chan, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 24, 2011
• First Posted: November 7, 2011
• Study Start: July 1, 2012
• Primary Completion: August 1, 2021
• Study Completion: December 1, 2023
• Last Updated: March 5, 2024
• Results First Posted: July 20, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)