Carcinoid TumorPhase 2NCT01466036
Cabozantinib in Advanced Pancreatic Neuroendocrine and Carcinoid Tumors
A Phase 2 study testing Cabozantinib in people with Carcinoid Tumor and Pancreatic Neuroendocrine Tumor, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoid Tumor, Pancreatic Neuroendocrine Tumor
- What is being tested?
- Cabozantinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2012to Dec 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 27Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02214
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: 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.
Read the 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.
- Conditions
- Carcinoid Tumor, Pancreatic Neuroendocrine Tumor
- Being tested
- Cabozantinib
- Keywords
- metastatic
- Medical subject headings
- Carcinoid Tumor, Adenoma, Islet Cell, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called XL184
60 mg QD orally in cycles of 28 days
| Study group | Role | What they receive |
|---|---|---|
| Metastatic or Unresectable PNET | Experimental | An anticipated 35 patients with pancreatic neuroendocrine tumors receiving cabozantinib Receives: Drug: Cabozantinib |
| Metastatic or Unresectable Carcinoid | Experimental | An anticipated 35 patients with advanced or metastatic carcinoid tumor receiving cabozantinib Receives: Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Progression-free survival was defined as time in months from initiation of treatment until disease progression by RECIST 1.1 criteria or death from any cause. Progressive disease by RECIST 1.1 criteria is defined as at least a 20% increase in the sum of the longest dimensions of target lesions, taking as reference the smallest sum of longest dimensions recorded since the treatment started; the appearance of one or more new lesions; unequivocal progression of existing non-target lesions.
Measured: 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)
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Measured: Median follow-up time of 89.1 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2011 (estimated)
- Study startJul 2012
- Primary completionAug 2021
- Study completionDec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoid TumorStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute
- Investigators
- Jennifer Chan, MD, MPH, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01466036
- Sponsor's protocol ID
- 11-274
- Status last verified
- Mar 2024
- First submitted
- 24 Oct 2011
- Last updated
- 5 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase II Study of Cabozantinib (XL184) in Advanced Pancreatic Neuroendocrine and Carcinoid Tumors
- ClinicalTrials.gov ID
- NCT01466036
- Acronym / sponsor ID
- 11-274
- Conditions
- Carcinoid Tumor, Pancreatic Neuroendocrine Tumor
- Keywords
- metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Aug 2021 (actual)
- Study completion
- Dec 2023 (actual)
- First posted
- 7 Nov 2011 (estimated)
- Results
- Posted 20 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metastatic or Unresectable PNET | Experimental | Drug: CabozantinibAn anticipated 35 patients with pancreatic neuroendocrine tumors receiving cabozantinib |
| Metastatic or Unresectable Carcinoid | Experimental | Drug: CabozantinibAn anticipated 35 patients with advanced or metastatic carcinoid tumor receiving cabozantinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CabozantinibAlso: XL18460 mg QD orally in cycles of 28 days | Drug | Metastatic or Unresectable Carcinoid, Metastatic or Unresectable PNET |
Primary outcome
Objective Response Rate (ORR)
Time frame: 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.
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.
2 secondary outcomes
Progression Free Survival (PFS)
Time frame: 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)
Time frame: Median follow-up time of 89.1 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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GEP-NET, Gastroenteropancreatic Neuroendocrine Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Chan, MD, MPH principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cabozantinib in people with Carcinoid Tumor and Pancreatic Neuroendocrine Tumor, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2024.