Cabozantinib in Advanced Pancreatic Neuroendocrine and Carcinoid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Jason Faris, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01466036
First received: October 24, 2011
Last updated: March 13, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Carcinoid Tumor
Pancreatic Neuroendocrine Tumor
Drug: Cabozantinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Phase II Study of Cabozantinib (XL184) in Advanced Pancreatic Neuroendocrine and Carcinoid Tumors

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Evaluate objective response rate of cabozantinib


Secondary Outcome Measures:
  • Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Determine progression-free and overall survival in patients receiving cabozantinib

  • Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Record number of patients with adverse events

  • Correlates of response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Define molecular correlates of response


Estimated Enrollment: 70
Study Start Date: July 2012
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metastatic or Unresectable Pancreatic Neuroendocrine Tumors
35 patients with pancreatic neuroendocrine tumors will be treated with cabozantinib
Drug: Cabozantinib
60 mg QD orally in cycles of 28 days
Other Name: XL184
Experimental: Metastatic or Unresectable Carcinoid Tumors
35 patients with advanced or metastatic carcinoid tumor
Drug: Cabozantinib
60 mg QD orally in cycles of 28 days
Other Name: XL184

Detailed Description:

Subjects will take cabozantinib orally, once per day, in cycles of 28 days.

During each cycle subjects will have the following procedures:

  • Physical examination, including measurement of weight and vital signs
  • Questions regarding any side effects
  • Blood sample (about 1 tablespoon) for routine laboratory tests of blood cell counts, blood chemistries, organ function and blood clotting
  • Blood sample (about 4 tablespoons) for research test to measure biomarkers to assess the response to study drug
  • Urine sample for routine urine tests to monitor health

On Day 15 (beginning of week 3) during the first 3 cycles:

  • Physical examination, including measurement of weight and vital signs
  • Questions regarding any side effects
  • Blood sample (about 1 tablespoon) for routine laboratory tests of blood cell counts, blood chemistries, organ function and blood clotting
  • Blood sample (about 4 tablespoons) for research test to measure biomarkers to assess the response to study drug Subjects will receive a CT scan or MRI every two cycles (every two months) to evaluate disease.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

    • 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
    • Urine Protein:Creatinine ratio of <1
    • Lipase < 1.5X upper limit of normal
    • Serum Albumin ≥ 2.8 g/dl
  • 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:

    • Active infection requiring systemic treatment
    • Serious non-healing wound/ulcer/bone fracture
    • History of organ transplant
    • Concurrent uncompensated hypothyroidism or thyroid dysfunction
    • History of major surgery within 4 weeks or minor surgical procedures within one week before randomization
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01466036

Contacts
Contact: Jason Faris, MD 617-724-4000 jfaris@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02214
Principal Investigator: Jason Faris, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Matthew Kulke, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Jason Faris, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Jason Faris, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01466036     History of Changes
Other Study ID Numbers: 11-274
Study First Received: October 24, 2011
Last Updated: March 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
metastatic

Additional relevant MeSH terms:
Carcinoid Tumor
Neuroendocrine Tumors
Adenoma, Islet Cell
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

ClinicalTrials.gov processed this record on July 22, 2014