First International Randomized Study in Malignant Progressive Pheochromocytoma and Paraganglioma (FIRSTMAPPP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2012 by Gustave Roussy, Cancer Campus, Grand Paris
Sponsor:
Collaborators:
National Cancer Institute, France
ENSAT-CANCER European Network for the Study of Adrenal Tumours
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier:
NCT01371201
First received: June 9, 2011
Last updated: December 18, 2013
Last verified: January 2012
  Purpose

The FIRSTMAPPP study is a randomized, double-blind, phase II, international, multicenter study which aims 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).


Condition Intervention Phase
Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)
Drug: Sunitinib
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: First International Randomized Study in Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)

Resource links provided by NLM:


Further study details as provided by Gustave Roussy, Cancer Campus, Grand Paris:

Primary Outcome Measures:
  • Progression-free survival at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Progression will be assessed by RECIST 1.1 performed every 3 months (centralized imaging)


Secondary Outcome Measures:
  • Objective Response Rates (ORR) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Duration of response (DR) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Overall Time to Progression (TTP) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Number of Adverse Events assessed using NCI -CTC V4 criteria [ Designated as safety issue: Yes ]
    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 [ Designated as safety issue: Yes ]
    Cardiovascular tolerance will be assessed by specific organisation for blood pressure monitoring

  • Bone Pain evaluation on the Visual Analog Scale [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: December 2011
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sunitinib
sunitinib 37.5 mg per day
Drug: Sunitinib
sunitinib 37.5 mg per day
Other Name: Sutent
Placebo Comparator: Placebo
Placebo 37.5 mg per day
Drug: Placebo
Placebo 37.5 mg per day

Detailed Description:

PRIMARY OBJECTIVE:

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).

SECONDARY OBJECTIVES:

  • 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).

EXPLORATORY OBJECTIVES:

-Identification of predictors of response as well as surrogate markers of overall survival is anticipated

  Eligibility

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

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  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: NCT01371201

Locations
France
Institut de Cancérologie Gustave roussy Recruiting
Villejuif, France, 94805
Contact: Eric Baudin, MD       eric.baudin@igr.fr   
Principal Investigator: Eric Baudin, MD         
Sub-Investigator: Martin Schlumberger, MD         
Sub-Investigator: Sophie Leboulleux, MD         
Sub-Investigator: Cécile Chougnet, MD         
Germany
Universitätsklinikum Würzburg Recruiting
Würburg, Germany, 97080
Contact: Martin FASSNACHT, MD    0931-201-39021      
Principal Investigator: Martin FASSNACHT, MD         
Italy
University of Padova Recruiting
Padova, Italy, 35128
Contact: Giusepe OPOCHER, MD    0498215503 ext +39      
Principal Investigator: Giusepe OPOCHER, MD         
Netherlands
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, GA, Netherlands, 6525
Contact: Henry TIMMERS, MD    0243614599 ext +31      
Principal Investigator: Henry TIMMERS, MD         
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
National Cancer Institute, France
ENSAT-CANCER European Network for the Study of Adrenal Tumours
Investigators
Principal Investigator: Eric Baudin, MD Gustave Roussy, Cancer Campus, Grand Paris
  More Information

Additional Information:
No publications provided

Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT01371201     History of Changes
Other Study ID Numbers: IGR2010/1715, 2010-024621-20, MSI/A110356-31
Study First Received: June 9, 2011
Last Updated: December 18, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Paraganglioma
Pheochromocytoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014