First International Randomized Study in Malignant Progressive Pheochromocytoma and Paraganglioma (FIRSTMAPPP)
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|ClinicalTrials.gov Identifier: NCT01371201|
Recruitment Status : Completed
First Posted : June 10, 2011
Last Update Posted : August 4, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)||Drug: Sunitinib Drug: Placebo||Phase 2|
To determine the efficacy of Sunitinib on the progression-free survival at 12 months in subjects with progressive malignant pheochromocytoma and paraganglioma treated with sunitinib at a starting dose of 37.5 mg daily (continuous dosing).
- To determine overall survival and progression free survival.
- To determine time to progression.
- To determine objective response rate at one year.
- To determine time to and duration of tumor response.
- To assess safety profile including a dedicated cardiovascular management (home-blood pressure monitoring, ECG and echocardiography).
-Identification of predictors of response as well as surrogate markers of overall survival is anticipated
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||78 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||First International Randomized Study in Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)|
|Actual Study Start Date :||December 22, 2011|
|Actual Primary Completion Date :||October 1, 2013|
|Actual Study Completion Date :||April 20, 2021|
sunitinib 37.5 mg per day
sunitinib 37.5 mg per day
Other Name: Sutent
Placebo Comparator: Placebo
Placebo 37.5 mg per day
Placebo 37.5 mg per day
- Progression-free survival at 12 months [ Time Frame: 12 months ]Progression will be assessed by RECIST 1.1 performed every 3 months (centralized imaging)
- Objective Response Rates (ORR) [ Time Frame: 12 months ]
- Duration of response (DR) [ Time Frame: 12 months ]
- Overall Time to Progression (TTP) [ Time Frame: 12 months ]
- Overall survival (OS) [ Time Frame: 12 months ]
- Number of Adverse Events assessed using NCI -CTC V4 criteria [ Time Frame: 12 months ]Number and description of adverse events and number of patients with adverse events according to NCI -CTC V4 criteria
- Number of patients with cardiovascular toxicity tolerance assessed by specific organisation for blood pressure monitoring [ Time Frame: 12 months ]Cardiovascular tolerance will be assessed by specific organisation for blood pressure monitoring
- Bone Pain evaluation on the Visual Analog Scale [ Time Frame: 12 months ]
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Diagnosis of malignant PPGL, based on imaging or biopsy evidence of metastases in liver, bones, lungs and or lymph nodes, combined with at least one of two further confirmatory diagnoses: 1. diagnosis of PPGL from histopathological review of resected or biopsied tissue performed by a skilled pathologist (centralized review will be performed in all cases either before enrolment in case of any doubt or during the study); or 2. in patients where tumor tissue is unavailable for formal pathological review, from combined biochemical and functional imaging evidence of PPGL (e.g., MIBG scintigraphy combined with consistently and highly elevated plasma or urine levels of metanephrines).
- Metastatic disease not amenable to surgical resection
- Pre-treated or not
- Whatever the genetic status (sporadic or inherited)
- Evaluable disease according to RECIST 1.1 criteria
- Progressing disease within 18 months at imaging prior to randomization according to RECIST. The recent scan indicating progression may be used as the screening scan if within 28 days of randomization
- ECOG performance status 0-2
- Life expectancy ≥ 6 months as prognosticated by the physician
- Age ≥18 years, no superior limit
- Adequate bone marrow reserve (Hb > 8, neutrophils ≥ 1500/mm³ and platelets ≥80.000/mm³)
- Effective contraception in pre-menopausal female and male patients
- Negative pregnancy test
- Patient´s signed written informed consent
- Ability to comply with the protocol procedures
- Ability to take oral medication
- Large or small cell-poorly differentiated neuroendocrine carcinoma according to WHO 2000 classification
- History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years.
- Severe renal (GFR <30ml/mn or nephrotic syndrome) or hepatic insufficiency (ALT / AST > 2.5 x ULN or ALT/AST >5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin > 2.5 x ULN)
- Patients with cardiac events within the previous 12 months, such as myocardial infarction (including severe/unstable angina pectoris), coronary/peripheral artery bypass graft, revascularization procedure symptomatic congestive heart failure (CHF, ejection fraction <45%), ), uncontrolled cardiac arrhythmia, clinically significant bradycardia, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
- Hypertension that cannot be controlled despite medications (>=160/95 mmHg despite optimal medical therapy)
- Abnormal cardiac function with 12 lead ECG. Ongoing cardiac dysrhythmias of NCI CTC grade >=2, atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec for males or >480 msec for females.
- Brain metastases (exception if stable and asymptomatic for more than 3 months)
- Pregnancy or breast feeding
- Previous treatment with the drug under study. Prior systemic treatment with any tyrosine kinase inhibitors or anti VEGF angiogenic inhibitors.
- Current treatment with another investigational drug.
- Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days, respectively prior to study drug administration
- Concomitant treatment with therapeutic doses of anticoagulants. Low dose warfarin (Coumadin) up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed as well as heparin-based anticoagulation
- Prior treatments with chemotherapy, immunotherapy, somatostatine analog therapy drug , thoracic radiotherapy within 4 weeks prior to inclusion
- Major surgery for any cause or local radiotherapy within one month prior to visit 1
- Liver embolisation therapy within the last 3 months prior visit 1 except if progression is demonstrated and embolised lesion not used as targets
- Unrecovered toxicity from any kind of therapy
- Active or suspected acute or chronic uncontrolled disease that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01371201
|Institut de Cancérologie Gustave roussy|
|Villejuif, France, 94805|
|Würburg, Germany, 97080|
|University of Padova|
|Padova, Italy, 35128|
|Radboud University Nijmegen Medical Centre|
|Nijmegen, GA, Netherlands, 6525|
|Principal Investigator:||Eric Baudin, MD||Gustave Roussy, Cancer Campus, Grand Paris|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Gustave Roussy, Cancer Campus, Grand Paris|
|Other Study ID Numbers:||
2010-024621-20 ( EudraCT Number )
MSI/A110356-31 ( Other Identifier: AFSSAPS )
|First Posted:||June 10, 2011 Key Record Dates|
|Last Update Posted:||August 4, 2022|
|Last Verified:||August 2022|
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Angiogenesis Modulating Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action