Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma

NCT00843037 | Completed Phase 2 Results DMC

• 1 other identifier: SNIPP
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 4

Brief 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. 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.

Conditions

Paraganglioma; Pheochromocytoma

Keywords

PARAGANGLIOMA; PHEOCHROMOCYTOMA; SUNITINIB; PHASE II; Metastatic or locally advanced malignant paraganglioma; Metastatic or locally advanced malignant pheochromocytoma

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  From time of enrollment until loss to follow-up or death (approximately 125 months for longest patient on treatment).

• Time to Progression

  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)

  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).

Study Arms (1)

Open label - Sunitinib

EXPERIMENTAL

Sunitinib, 50mg daily, once daily for 4 weeks followed by a 2-week break

Drug: Sunitinib

Interventions

Sunitinib DRUG

50 mg oral dose daily for 4 weeks, 2 week rest period (repeating 6 week cycles)

Also known as: Sunitinib malate (suntinib; SU11248, SU011248, Sutent®)

Open label - Sunitinib

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Pfizer: collaborator

Study Sites (4)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Hôpital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

University Medical Centre Groningen

Groningen, Netherlands

Location

MeSH Terms

Conditions

Paraganglioma; Pheochromocytoma; Neoplasm Metastasis

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Some patients did not have genetic testing and this trial is not able to define prognostic or predictive biomarkers due to small numbers; genetic panel testing varied between institutions and during study period; plasma metanephrine analysis not performed throughout study; only total and not fractionated urinary metanephrines were available; incomplete biochemical interpretation; some standard practices now were not integrated when study initiated in May 2009

Results Point of Contact

• Title: Dr. Jennifer Knox, PI
• Organization: University Health Network

jennifer.knox@uhn.ca

(416) 946-2000

Study Officials

• Jennifer Knox, MD, FRCPC

  The Princess Margaret Cancer Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 13, 2009
• Study Start: February 1, 2009
• Primary Completion: March 14, 2022
• Study Completion: March 14, 2022
• Last Updated: October 17, 2024
• Results First Posted: October 17, 2024

Record last verified: 2024-10

Locations

CA (3); NL (1)