First International Randomized Study in Malignant Progressive Pheochromocytoma and Paraganglioma

NCT01371201 | Completed Phase 2 DMC

• 3 other identifiers: IGR2010/17152010-024621-20MSI/A110356-31
• Study Type: interventional
• Target: 78
• Locations: 4 countries
• Sites: 4

Brief Summary

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).

Conditions

Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 12 months

  Progression will be assessed by RECIST 1.1 performed every 3 months (centralized imaging)

  12 months

Secondary Outcomes (7)

• Objective Response Rates (ORR)

  12 months

• Duration of response (DR)

  12 months

• Overall Time to Progression (TTP)

  12 months

• Overall survival (OS)

  12 months

• Number of Adverse Events assessed using NCI -CTC V4 criteria

  12 months

Study Arms (2)

Sunitinib

EXPERIMENTAL

sunitinib 37.5 mg per day

Drug: Sunitinib

Placebo

PLACEBO COMPARATOR

Placebo 37.5 mg per day

Drug: Placebo

Interventions

Sunitinib DRUG

sunitinib 37.5 mg per day

Also known as: Sutent

Sunitinib

Placebo DRUG

Placebo 37.5 mg per day

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• National Cancer Institute, France: collaborator
• European Network for the Study of Adrenal Tumours: collaborator

Study Sites (4)

Institut de Cancérologie Gustave roussy

Villejuif, 94805, France

Location

Universitätsklinikum Würzburg

Würburg, 97080, Germany

Location

University of Padova

Padua, 35128, Italy

Location

Radboud University Nijmegen Medical Centre

Nijmegen, GA, 6525, Netherlands

Location

Related Publications (2)

• Baudin E, Goichot B, Berruti A, Hadoux J, Moalla S, Laboureau S, Nolting S, de la Fouchardiere C, Kienitz T, Deutschbein T, Zovato S, Amar L, Haissaguerre M, Timmers H, Niccoli P, Faggiano A, Angokai M, Lamartina L, Luca F, Cosentini D, Hahner S, Beuschlein F, Attard M, Texier M, Fassnacht M; ENDOCAN-COMETE; ENSAT Networks. Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial. Lancet. 2024 Mar 16;403(10431):1061-1070. doi: 10.1016/S0140-6736(23)02554-0. Epub 2024 Feb 22.

  PMID: 38402886 DERIVED

• Fankhauser M, Bechmann N, Lauseker M, Goncalves J, Favier J, Klink B, William D, Gieldon L, Maurer J, Spottl G, Rank P, Knosel T, Orth M, Ziegler CG, Aristizabal Prada ET, Rubinstein G, Fassnacht M, Spitzweg C, Grossman AB, Pacak K, Beuschlein F, Bornstein SR, Eisenhofer G, Auernhammer CJ, Reincke M, Nolting S. Synergistic Highly Potent Targeted Drug Combinations in Different Pheochromocytoma Models Including Human Tumor Cultures. Endocrinology. 2019 Nov 1;160(11):2600-2617. doi: 10.1210/en.2019-00410.

  PMID: 31322702 DERIVED

Related Links

• Sponsor website

MeSH Terms

Conditions

Paraganglioma

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

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

Study Officials

• Eric Baudin, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2011
• First Posted: June 10, 2011
• Study Start: December 22, 2011
• Primary Completion: October 1, 2013
• Study Completion: April 20, 2021
• Last Updated: August 4, 2022

Record last verified: 2022-08

Locations

IT (1); NL (1); DE (1); FR (1)