Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)Phase 2FIRSTMAPPPNCT01371201
First International Randomized Study in Malignant Progressive Pheochromocytoma and Paraganglioma
A Phase 2 study testing Sunitinib in people with Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL), run by Gustave Roussy, Cancer Campus, Grand Paris at 4 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)
- What is being tested?
- Sunitinib
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 22 Dec 2011to 20 Apr 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, GA, 6525
About this study
Official title: First International Randomized Study in Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)
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).
Read the 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
- Being tested
- Sunitinib, Placebo
- Medical subject headings
- Paraganglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Sutent
sunitinib 37.5 mg per day
PlaceboDrug
Placebo 37.5 mg per day
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib | Experimental | sunitinib 37.5 mg per day Receives: Drug: Sunitinib |
| Placebo | Placebo comparator | Placebo 37.5 mg per day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival at 12 months
Progression will be assessed by RECIST 1.1 performed every 3 months (centralized imaging)
Measured: 12 months
Secondary outcomes (7)
Objective Response Rates (ORR)
Measured: 12 months
Duration of response (DR)
Measured: 12 months
Overall Time to Progression (TTP)
Measured: 12 months
Overall survival (OS)
Measured: 12 months
Number of Adverse Events assessed using NCI -CTC V4 criteria
Number and description of adverse events and number of patients with adverse events according to NCI -CTC V4 criteria
Measured: 12 months
Number of patients with cardiovascular toxicity tolerance assessed by specific organisation for blood pressure monitoring
Cardiovascular tolerance will be assessed by specific organisation for blood pressure monitoring
Measured: 12 months
Bone Pain evaluation on the Visual Analog Scale
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2011 (estimated)
- Study start22 Dec 2011
- Primary completion1 Oct 2013
- Study completion20 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)Studies of the same condition, open and under way.
- More trials run by Gustave Roussy, Cancer Campus, Grand ParisThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France, European Network for the Study of Adrenal Tumors
- Responsible party
- Sponsor
- Investigators
- Eric Baudin, MD, Principal investigator, Gustave Roussy, Cancer Campus, Grand Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01371201
- Sponsor's protocol ID
- IGR2010/1715
- Other IDs
- 2010-024621-20, MSI/A110356-31
- Acronym
- FIRSTMAPPP
- Status last verified
- Aug 2022
- First submitted
- 9 Jun 2011
- Last updated
- 4 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 38402886Fankhauser 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.
PubMed 31322702
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First International Randomized Study in Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL)
- ClinicalTrials.gov ID
- NCT01371201
- Acronym / sponsor ID
- FIRSTMAPPP / IGR2010/1715
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Collaborators
- National Cancer Institute, France, European Network for the Study of Adrenal Tumors
- Study start
- 22 Dec 2011 (actual)
- Primary completion
- 1 Oct 2013 (actual)
- Study completion
- 20 Apr 2021 (actual)
- First posted
- 10 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Experimental | Drug: Sunitinibsunitinib 37.5 mg per day |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 37.5 mg per day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SunitinibAlso: Sutentsunitinib 37.5 mg per day | Drug | Sunitinib |
| PlaceboPlacebo 37.5 mg per day | Drug | Placebo |
Primary outcome
Progression-free survival at 12 months
Time frame: 12 months
Progression will be assessed by RECIST 1.1 performed every 3 months (centralized imaging)
7 secondary outcomes
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 of patients with cardiovascular toxicity tolerance assessed by specific organisation for blood pressure monitoring
Time frame: 12 months
Bone Pain evaluation on the Visual Analog Scale
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2022.
- Derived from this study: PubMed 38402886Baudin 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.
- Derived from this study: PubMed 31322702Fankhauser 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.
- Sponsor websiteLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Baudin, MD principal investigator
Gustave Roussy, Cancer Campus, Grand Paris
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sunitinib in people with Malignant Progressive Pheochromocytoma and Paraganglioma (PPGL), run by Gustave Roussy, Cancer Campus, Grand Paris at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France, Germany, Italy, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival at 12 months (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01371201, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2022.