ParagangliomaPhase 2SNIPPNCT00843037
Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma
A Phase 2 study testing Sunitinib in people with Paraganglioma and Pheochromocytoma, run by University Health Network, Toronto at 4 sites in 2 countries.
Trial summary
This is an open-label phase II study of an investigational drug, sunitinib malate in patients with advanced malignant paraganglioma or phaeochromocytoma cancer. Paragangliomas (PGs) are tumours that arise from the para-sympathetic system in the head and neck and sympathetic system in the thorax and abdomen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paraganglioma, Pheochromocytoma
- What is being tested?
- Sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Feb 2009to 14 Mar 2022
- Phase
- Phase 2
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
- Histologically or cytologically confirmed diagnosis of malignant paraganglioma or pheochromocytoma and either evidence of metastases or unresectability.
- Evidence of recent disease progression (radiological, biochemical, symptomatic).
- Measurable disease defined as that which can be measured in at least one dimension with a minimum size of 10 mm by CT scan.
- ECOG 0-2.
- Life expectancy of greater than 24 weeks.
- Age > 18 years.
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- Patients must have normal organ and marrow function.
- Patients must have PT/INR/PTT within 1.2 X the upper limit
- Patients may have had prior radiation therapy. A minimum of 28 days must have elapsed between the end of radiotherapy and registration onto the study.
- Previous Surgery: Previous major surgery is permitted provided that it has been at least 28 days prior to patient registration
- Laboratory Requirements Parameter Limit granulocytes (AGC) > 1.5 x 109/L platelets > 100 x 109/L bilirubin < 1.5XULN AST and ALT < 2.5 x ULN Amylase <1.5XULN Lipase <1.5XULN Calcium < 3 mmol/L creatinine < 2.0XULN
Who cannot join
- History of other malignancies.
- Patients with known brain metastases.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib.
- Patients receiving concurrent treatment with other anti-cancer therapy given for paraganglioma or pheochromocytoma or other therapy or other investigational anticancer agents.
- Patients who have received prior treatment with any other antiangiogenic agent or multi-targeted tyrosine kinase inhibitors are ineligible.
- Patients with any of the following cardiovascular findings are to be excluded:
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- QTc prolongation or other significant ECG abnormalities.
- Current or history of Class III or IV heart failure as defined by the NYHA functional classification system
- Patients with prior anthracycline exposure, previous central thoracic radiation that included heart in radiation port, or a history of NYHA Class II cardiac function.
- Poorly controlled hypertension
- Myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry
- History of venous thrombosis or pulmonary embolism in the past 3 months
- History of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry
- Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin
- Patients with bowel obstruction or any condition that impairs their ability to swallow and retain sunitinib tablets.
- Use of agents with proarrhythmic potential is not permitted during the study.
- Must be able to stop prohibited selected CYP3A4 inhibitors/inducers prior to starting sunitinib
- Patients with pre-existing hypothyroidism prior to enrolment are ineligible unless they are euthyroid on medication.
- Pregnant or lactating women, positive pregnancy test, women of childbearing potential who do not agree to use adequate contraception prior to study entry and for the duration of study participation.
- Known HIV-positive patients on combination antiretroviral therapy
- Greater than +1 proteinuria on urinary dipstick if also >1g urinary protein/24hrs
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Canada3 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Hôpital Notre-Dame du CHUM
Montreal, Quebec, H2L 4M1
University Health Network, Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
About this study
Official title: A Investigator Initiated Phase II Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma
This is an open-label phase II study of an investigational drug, sunitinib malate in patients with advanced malignant paraganglioma or phaeochromocytoma cancer. Paragangliomas (PGs) are tumours that arise from the para-sympathetic system in the head and neck and sympathetic system in the thorax and abdomen. Paragangliomas that secrete hormones (catecholamines) from the adrenal glands are called pheochromocytomas (PCs). In this study, patients whose disease has advanced or spread despite prior standard therapy, will receive sunitinib for 4-weeks followed by a 2-week rest period, for up to 12 months, in the absence of disease progression. Sunitinib is an investigational drug, which has been shown to shrink tumours in several tumour models. The study will evaluate the efficacy as well as the toxicity profile of sunitinib when used as an alternative treatment for patients with PG/PC tumours.
Read the detailed description
This study will be a single arm, open-label, phase II trial of sunitinib in patients with metastatic or locally advanced malignant paraganglioma or phaeochromocytoma. Oral sunitinib (50 mg) will be administered to all patients daily for the first four weeks of a six week study cycle, followed by a 2-week rest. Patients will be assessed for response to study treatment using MRI/CT scans as well as bio-chemical tests, and will receive the study treatment for up to 12 months or until disease progression.
Primary study outcomes include:
To assess the efficacy (response rate) of sunitinib given orally daily for 4 out of every 6 weeks in patients with advanced or metastatic paraganglioma/ pheochromocytoma.
To assess the toxicity of sunitinib in patients with advanced or metastatic paraganglioma/ pheochromocytoma.
To document effects of sunitinib on markers of biochemical activity of advanced or metastatic paraganglioma/ pheochromocytoma.
- Conditions
- Paraganglioma, Pheochromocytoma
- Being tested
- Sunitinib
- Keywords
- PARAGANGLIOMA, PHEOCHROMOCYTOMA, SUNITINIB, PHASE II, Metastatic or locally advanced malignant paraganglioma, Metastatic or locally advanced malignant pheochromocytoma
- Medical subject headings
- Paraganglioma, Pheochromocytoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Sunitinib malate (suntinib; SU11248, SU011248, Sutent®)
50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)
| Study group | Role | What they receive |
|---|---|---|
| Open label - Sunitinib | Experimental | Sunitinib, 50mg daily, once daily for 4 weeks followed by a 2-week break Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate (CBR) Which is Defined as Either a Partial Response (PR) Complete Response (CR) or Stable Disease (SD) for ≥ 12 Weeks Measured Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
The primary endpoint of this study was disease control rate (DCR) defined as a partial response (PR), complete response (CR), or stable disease maintained for ≥12 weeks from the initiation of treatment. Tumour response to sunitinib was assessed as per RECIST 1.1 using CT-imaging. Clinically apparent lesions needed to be >10mm by calliper measurement to be included as targets. The primary endpoint was met despite closing to accrual early.
Measured: Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).
Secondary outcomes (4)
Biochemical Response (BCR) of > 20% Drop in 24-hour Urinary Metanephrines, Catecholamines or Serum Chromogranin A, Sustained for > 12-week Period
Biochemical and symptom changes: timed urinary catecholamine collection over 24 h included measurements of norepinephrine, epinephrine, dopamine and total metanephrines.
Measured: Within 7 days of study registration and every 12 weeks (2 cycles) up to treatment discontinuation (an average of 13.5 6-week cycles or about 1.5 years).
Overall Survival
The median overall survival
Measured: From time of enrollment until loss to follow-up or death (approximately 125 months for longest patient on treatment).
Time to Progression
Median Progression-Free Survival (PFS)
Measured: Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).
Overall Response Rate (PR) + (CR)
Overall response rate (PR) + (CR) of participants
Measured: Every 12 weeks (2 cycles) up to disease progression or study discontinuation (an average of 13.5 6-week cycles or about 1.5 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completion14 Mar 2022
- Study completion14 Mar 2022
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 ParagangliomaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Jennifer Knox, MD, FRCPC, Principal investigator, The Princess Margaret Cancer Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00843037
- Sponsor's protocol ID
- SNIPP
- Acronym
- SNIPP
- Status last verified
- Oct 2024
- First submitted
- 12 Feb 2009
- Last updated
- 17 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes