Malignant Adrenal Gland PheochromocytomaPhase 2NCT03008369
Lenvatinib in Treating Patients With Metastatic or Advanced Pheochromocytoma or Paraganglioma That Cannot Be Removed by Surgery
A Phase 2 study testing Laboratory Biomarker Analysis, Lenvatinib and Quality-of-Life Assessment in people with Malignant Adrenal Gland Pheochromocytoma and Malignant Paraganglioma, run by Mayo Clinic at 1 site in United States.
Trial summary
This phase II trial studies how well lenvatinib works in treating patients with pheochromocytoma or paraganglioma that has spread to other places in the body or cannot be removed by surgery. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Adrenal Gland Pheochromocytoma, Malignant Paraganglioma, Metastatic Adrenal Gland Pheochromocytoma
- What is being tested?
- Laboratory Biomarker Analysis, Lenvatinib and Quality-of-Life Assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 31 May 2017to 28 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically or cytologically confirmed malignant secretory or non-secretory pheochromocytoma or paraganglioma that is unresectable and deemed inappropriate for alternative local regional therapeutic approaches
- Measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Life expectancy > 24 weeks
- Absolute neutrophil count (ANC) >= 1500/mm^3
- White blood cell (WBC) count >= 3,000/mm^3
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- Platelet count >= 100,000/mm^3
- Hemoglobin >= 9.0 g/dL (5.6 mmol/L); NOTE: transfusions are not allowed =< 7 days prior to registration
- Total bilirubin =< 1.5 X upper limit of normal (ULN) (or total bilirubin =< 3.0 X ULN with direct bilirubin =< 1.5 X ULN in patients with well-documented Gilbert's Syndrome)
- Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X ULN
- Creatinine =< 1.5 x ULN
- Urine protein/creatinine ratio =< 1 OR 24-hour urine protein < 1.5 gram
- Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Blood pressure (BP) < 150 mmHg (systolic) and < 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 150/90 mmHg; NOTE: all patients with secretory pheochromocytoma or paraganglioma are REQUIRED to: 1) be evaluated in consultation by a hypertension specialist with specific experience in the management of hypertension in the setting of catecholamine-secreting tumors (usually an endocrinologist, nephrologist, or a cardiologist), and in the setting of hormone-associated hypertension) receive alpha- and beta-adrenergic blockade for at least 7-14 days prior to initiation of lenvatinib; the hypertension specialist of record for each patient should be committed to closely following the patient during the clinical study with evaluation by said specialist required at cycle 1 and 2 and thereafter on an as needed basis
- Provide written informed consent
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Ability to complete questionnaire(s) by themselves or with assistance
Who cannot join
- Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery =< 21 days prior to registration or kinase inhibitor therapy =< 14 days prior to registration or failure to recover from toxicities (to grade 1 or below) from treatment; NOTE: concurrent therapy with octreotide is allowed providing that tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed; NOTE: an unlimited number of prior chemotherapeutic or biologic therapies for malignant pheochromocytoma or paraganglioma is permitted; this includes prior anti-angiogenesis therapies such as tyrosine kinase inhibitors
- Active or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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- Receiving any other investigational agent
- Current use of warfarin for any reason; NOTE: if patient can be safely transitioned to another anticoagulant, they may be eligible provided other criteria are satisfied
- Any of the following:
- Correct QT (QTc) prolongation (defined as a QTc interval >= 500 msecs)
- Left ventricular ejection fraction (LVEF) < institutional lower limits of normal (LLN)
- Frequent ventricular ectopy
- Evidence of ongoing myocardial ischemia
- Receiving any medications or substances with risk of torsades de pointes; NOTE: medications or substances with known risk of torsades de pointes are prohibited; consult pharmacist for review if needed
- Known active and/or untreated brain metastases
- Known severe allergic or other prohibitive reactions to other tyrosine kinase inhibitors (TKI)
- Prior treatment with lenvatinib
- Any of the following conditions:
- Active peptic ulcer disease
- Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
- History of new abdominal fistula, gastrointestinal perforation or intra-abdominal abscess =< 84 days prior to registration; NOTE: enrollment of patients with chronic/canalized fistulous tracts (present for > 84 days) is allowed
- Serious or non-healing wound, ulcer, or bone fracture
- History of familial QTc prolongation syndrome
- Any of the following conditions =< 6 months prior to registration:
- Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
- Serious or unstable cardiac arrhythmia
- Admission for unstable angina or myocardial infarction
- Cardiac angioplasty or stenting
- Coronary artery bypass graft surgery
- Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation =< 30 days
- Arterial thrombosis
- Symptomatic peripheral vascular disease
- Other active malignancy =< 2 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer; NOTE: adjuvant anti-estrogen/hormonal therapy for breast cancer is allowed
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Lenvatinib in Metastatic or Advanced Pheochromocytoma and Paraganglioma
This phase II trial studies how well lenvatinib works in treating patients with pheochromocytoma or paraganglioma that has spread to other places in the body or cannot be removed by surgery. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the anti-tumor activity of lenvatinib (overall response rate; [ORR]) in patients with metastatic or advanced unresectable pheochromocytomas and paragangliomas.
SECONDARY OBJECTIVES:
- To determine progression-free survival (PFS). II. To determine overall survival (OS). III. To determine duration of tumor response. IV. To determine safety and tolerability of lenvatinib. V. To assess patient reported quality of life using EuroQol Five-Dimensional Five Level Scale Questionnaire (EQ-5D-5L) and Functional Assessment of Cancer Therapy-General (FACT-G).
TERTIARY OBJECTIVES:
- For patients with secretory tumors, to examine changes in plasma metanephrine levels and urinary catecholamine and/or metanephrine levels.
II. For patients with secretory tumors, to examine whether lenvatinib-induced changes in plasma metanephrines and urinary catecholamine and/or metanephrine levels during the first cycle of treatment may be associated with objective tumor response.
III. To examine associations between tumor response and somatic mutational status in archived tumors, or germline mutational status (presence of SDHD, SDHB, RET, VHL, neurofibromatosis type-1).
OUTLINE:
Patients receive lenvatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 or 6 months for up to 5 years.
- Conditions
- Malignant Adrenal Gland Pheochromocytoma, Malignant Paraganglioma, Metastatic Adrenal Gland Pheochromocytoma
- Being tested
- Laboratory Biomarker Analysis, Lenvatinib, Quality-of-Life Assessment
- Medical subject headings
- Paraganglioma, Extra-Adrenal, Pheochromocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
LenvatinibDrug
Also called E7080, ER-203492-00, Multi-Kinase Inhibitor E7080
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (lenvatinib) | Experimental | Patients receive lenvatinib PO once daily on days 1-28. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Lenvatinib; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed Tumor Response Rate
Will be defined as 100% times the number of eligible patients who has started lenvatinib and whose objective tumor status was a complete response or partial response on 2 consecutive evaluations at least 4 weeks apart (using Response Evaluation Criteria in Solid Tumors version 1.1 criteria) divided by the number of eligible patients who has started lenvatinib. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Measured: Monthly, up to 17 months.
Secondary outcomes (5)
Duration of Tumor Response
Will be estimated using the Kaplan-Meier method.
Measured: Every month until off treatment, at off treatment, every 3 months until PD, at PD, every 6 months after PD up to 17 months
Patients Evaluable for Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Adverse Events are fully reported in the adverse event section of the results. All adverse events will be graded. For each type of adverse event classified as either possibly, probably, or definitely related to study treatment, the proportion of patients experiencing a severe (grade 3 or higher) adverse event will be noted per cycle. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns.
Measured: Monthly, up to 17 months.
Overall Survival Time
Will be estimated using the Kaplan-Meier method.
Measured: Every month until off treatment, at off treatment, every 3 months until PD, at PD, every 6 months after PD up to 17 months
Progression-free Survival
Will be estimated using the Kaplan-Meier method.
Measured: Every month until off treatment, at off treatment, every 3 months until PD, at PD or up to 17 months
Quality of Life Assessed by EQ-5D and FACT-G
Descriptive statistics, and scatter plots will form the basis of presentation of these data both overall and by other outcomes (toxicity, response and survival measures). Correlations between the quality of life outcomes and other outcome measures will be carried out by standard parametric and nonparametric tests (e.g. Pearson's and Spearman's rho). Comparison between continuous variables will be made with Wilcoxon rank sum tests, Fisher's exact tests will be used to determine differences between categorical variables, and Log-rank test will be used to test differences between time-to-event ou
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2017 (estimated)
- Study start31 May 2017
- Primary completion1 Dec 2020
- Study completion28 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Adrenal Gland PheochromocytomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ashish Chintakuntlawar, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03008369
- Sponsor's protocol ID
- MC1575
- Other IDs
- NCI-2016-02032, MC1575, P30CA015083
- Status last verified
- Jan 2024
- First submitted
- 28 Dec 2016
- Last updated
- 20 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Lenvatinib in Metastatic or Advanced Pheochromocytoma and Paraganglioma
- ClinicalTrials.gov ID
- NCT03008369
- Acronym / sponsor ID
- MC1575
- Conditions
- Malignant Adrenal Gland Pheochromocytoma, Malignant Paraganglioma, Metastatic Adrenal Gland Pheochromocytoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 31 May 2017 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 28 Sep 2022 (actual)
- First posted
- 2 Jan 2017 (estimated)
- Results
- Posted 14 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well lenvatinib works in treating patients with pheochromocytoma or paraganglioma that has spread to other places in the body or cannot be removed by surgery. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the anti-tumor activity of lenvatinib (overall response rate; [ORR]) in patients with metastatic or advanced unresectable pheochromocytomas and paragangliomas.
SECONDARY OBJECTIVES:
- To determine progression-free survival (PFS). II. To determine overall survival (OS). III. To determine duration of tumor response. IV. To determine safety and tolerability of lenvatinib. V. To assess patient reported quality of life using EuroQol Five-Dimensional Five Level Scale Questionnaire (EQ-5D-5L) and Functional Assessment of Cancer Therapy-General (FACT-G).
TERTIARY OBJECTIVES:
- For patients with secretory tumors, to examine changes in plasma metanephrine levels and urinary catecholamine and/or metanephrine levels.
II. For patients with secretory tumors, to examine whether lenvatinib-induced changes in plasma metanephrines and urinary catecholamine and/or metanephrine levels during the first cycle of treatment may be associated with objective tumor response.
III. To examine associations between tumor response and somatic mutational status in archived tumors, or germline mutational status (presence of SDHD, SDHB, RET, VHL, neurofibromatosis type-1).
OUTLINE:
Patients receive lenvatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 or 6 months for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (lenvatinib) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Lenvatinib, Other: Quality-of-Life AssessmentPatients receive lenvatinib PO once daily on days 1-28. Courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically or cytologically confirmed malignant secretory or non-secretory pheochromocytoma or paraganglioma that is unresectable and deemed inappropriate for alternative local regional therapeutic approaches
- Measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Life expectancy > 24 weeks
- Absolute neutrophil count (ANC) >= 1500/mm^3
Key exclusion criteria (33 listed)
- Any of the following:
- Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery =< 21 days prior to registration or kinase inhibitor therapy =< 14 days prior to registration or failure to recover from toxicities (to grade 1 or below) from treatment; NOTE: concurrent therapy with octreotide is allowed providing that tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed; NOTE: an unlimited number of prior chemotherapeutic or biologic therapies for malignant pheochromocytoma or paraganglioma is permitted; this includes prior anti-angiogenesis therapies such as tyrosine kinase inhibitors
- Active or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent
- Current use of warfarin for any reason; NOTE: if patient can be safely transitioned to another anticoagulant, they may be eligible provided other criteria are satisfied
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (lenvatinib) |
| LenvatinibAlso: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080Given PO | Drug | Treatment (lenvatinib) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (lenvatinib) |
Primary outcome
Confirmed Tumor Response Rate
Time frame: Monthly, up to 17 months.
Will be defined as 100% times the number of eligible patients who has started lenvatinib and whose objective tumor status was a complete response or partial response on 2 consecutive evaluations at least 4 weeks apart (using Response Evaluation Criteria in Solid Tumors version 1.1 criteria) divided by the number of eligible patients who has started lenvatinib. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
5 secondary outcomes
Duration of Tumor Response
Time frame: Every month until off treatment, at off treatment, every 3 months until PD, at PD, every 6 months after PD up to 17 months
Patients Evaluable for Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Time frame: Monthly, up to 17 months.
Overall Survival Time
Time frame: Every month until off treatment, at off treatment, every 3 months until PD, at PD, every 6 months after PD up to 17 months
Progression-free Survival
Time frame: Every month until off treatment, at off treatment, every 3 months until PD, at PD or up to 17 months
Quality of Life Assessed by EQ-5D and FACT-G
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
Ashish Chintakuntlawar principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis, Lenvatinib and Quality-of-Life Assessment in people with Malignant Adrenal Gland Pheochromocytoma and Malignant Paraganglioma, run by Mayo Clinic at 1 site in United States.
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 17 inclusion and 33 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 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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?
Yes. Results are posted in the registry (first posted 14 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Confirmed Tumor Response Rate (time frame: Monthly, up to 17 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Feb 2024.