PheochromocytomaPhase 2NCT00028106
131MIBG to Treat Malignant Pheochromocytoma
A Phase 2 study testing [131]I-MIBG, 6-[18F]Fluorodopamine and [123]I-MIBG in people with Pheochromocytoma, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
This study will evaluate the effectiveness of 131MIBG in treating malignant pheochromocytoma and whether sensitization medications improve the response to treatment. Pheochromocytoma is a rare type of tumor that usually occurs in the adrenal glands. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pheochromocytoma
- What is being tested?
- [131]I-MIBG, 6-[18F]Fluorodopamine and [123]I-MIBG
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2001to 8 Jan 2007
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will have malignant pheochromocytoma defined as a locally-invasive adrenal tumor and/or a metastatic extra-adrenal tumor located in tissues where chromaffin cells are not normally present.
- Histologic proof of pheochromocytoma is not required but the nature of the tumor will be confirmed either by surgical pathological diagnosis or by biochemical measurements.
- Patients may have single or multiple tumors. There must be at least one discrete metastatic tumor that can be detected and measured by CT or MRI. Metastatic tumor sites may or may not be resectable.
- The tumor(s) must concentrate [131]I-MIBG.
- Tumors may be stable, or be growing or increasing in number at the time of this study. There will be no limit on tumor size.
- Patients will be adults, male or female, and not be limited to any ethnic or racial groups.
- Patients will have a Karnofsky score of at least 60%.
- Women of childbearing potential must practice an effective method of birth control while participating in the study. All men must also practice an effective method of birth control while in the study.
Who cannot join
- Pregnant or lactating women will be excluded. A positive pregnancy test will exclude the patient from further participation in this protocol.
- Children (less than 18 years of age) and patients older than 70 years of age will be excluded.
- Patients will be further excluded if they have:
- Impaired cardiovascular function (ejection fraction of less than 40%, symptomatic congestive heart failure, sustained blood pressure over 190/100, angina pectoris);
- Abnormal coagulation parameters (PT and PTT elevated by 30% above the normal);
- Hematocrit below 30%, hemoglobin below 10 g/dl, white blood cell count below 3000 per mm(3), absolute neutrophil count below 1000 per mm(3), platelet count below 100,000 per mm(3));
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- Any reason not to accept blood transfusions which may be needed as treatment for myelotoxicity from experimental [131I]-MIBG therapy;
- Liver enzymes greater than 2.5 times the upper limit of normal; serum bilirubin greater than 1.5 times the upper limit of normal.
- Renal dysfunction (serum creatinine greater than 2.0 mg/dl);
- Life expectancy less than 3 months;
- Weight over 136 kg, This is the limit for the scanning tables;
- Combined blood withdrawal greater than 450 ml during the six weeks preceding the study;
- Impaired mental capacity that precludes written informed consent.
- Prior experimental treatment with [131I]-MIBG, [90Y]-octreotide (an alternative agent being investigated to treat pheochromocytoma), or chemotherapy will exclude the patient, if this treatment was received in the previous 3 months provided the patient meets all other entry criteria.
- Labetalol, reserpine, calcium channel blockers, tricyclic anti-depressants, phenylephrine, phenylpropanolamine, pseudoephedrine, ephedrine, and some atypical anti-depressants/anti-psychotics interfere with uptake of [131I]-MIBG by pheochromocytomas. If a patient cannot change to a non-interfering pharmaceutical, they will be ineligible for the study.
- Due to the potiential immunosuppressive effect of radiation therapy, patients with positive HIV are excluded from this study. Patients with hepatitis B or hepatitis C are excluded due to the potential of liver toxicity.
- Patients who have received high dose chemotherapy with bone marrow transplant therapy or stem cell infusion are excluded.
- Patients who have received radiation therapy to the pelvis and/or spine are excluded. Local radiation therapy to one site (excluding pelvis/spine) will be permitted provided that at least 1 year has lapsed and the patient meets all other entry criteria.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: (131)I-Metaiodobenzylguanidine Treatment of Malignant Pheochromocytoma
This study will evaluate the effectiveness of 131MIBG in treating malignant pheochromocytoma and whether sensitization medications improve the response to treatment. Pheochromocytoma is a rare type of tumor that usually occurs in the adrenal glands. The tumor cells release chemicals like adrenaline that can cause large increases in blood pressure and pulse rate, with serious health consequences. Tumor in the adrenal glands usually can be removed surgically, but if the pheochromocytoma is malignant-i.e., has spread to many sites in the body-or is located in places where surgery is difficult or impossible, no satisfactory treatment is available. 131MIBG is a combination of an adrenaline-like chemical and a radioactive form of iodine. The 131MIBG attaches to the tumor cells and the high concentration of radioactive iodine kills them. Previous studies using 131MIBG to treat pheochromocytoma had a 36% response rate in terms of complete or partial improvement. This study will examine whether adding other sensitization medications to the 131MIBG treatment regimen will enhance its effectiveness in reducing the size and number of tumors.
Patients 18 years of age and older with malignant or inoperable pheochromocytoma may be eligible for this 18-month study. Candidates will be screened with various tests and procedures, which may include a medical history, physical examination, blood and urine tests, lung function studies, electrocardiogram, echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and bone scans and other scans using radioactive MIBG and octreotide.
Read more
Participants will be randomly assigned to one of two treatment groups: 1) 131MIBG plus sensitization medications, or 2) 131MIBG alone. All patients will be hospitalized 3 to 5 days for each 131MIBG treatment. The drug will be infused through a vein (intravenously, or I.V.) over 10 to 30 minutes. Patients will receive up to 3 treatments, separated by at least 3 months. All patients will also take potassium to protect the thyroid gland from radioactive iodine generated by the 131MIBG. The potassium is taken twice a day for 30 days, beginning the day before the 131MIBG treatment. Patients in the sensitization group will receive the following additional drugs for sensitization: methylprednisolone, intravenously a few minutes before 131MIBG treatment; Roaccutan, by mouth (capsules) twice a day for 6 weeks before treatment; Demser, by mouth 3 times a week for 1 week before treatment, and Carbidopa, by mouth every 6 hours for 4 days before treatment.
After each treatment, patients will have a clinical evaluation and periodic blood tests to check for adverse side effects of radiotherapy. Follow-up visits at NIH will be scheduled at 12 and 18 months after the first 131MIBG treatment for clinical, laboratory and imaging tests. Patients who had tumors in the lungs before treatment will have lung function tests 1, 3, and 6 months after each treatment. CT, MRI 131MIBG, and PET scanning will be done 1 week before each treatment.
Patients who have tumors that have grown by more than 25% and none that have shrunk by more than 50% or who have developed one or more new tumors while on 131MIBG treatment will be taken off the study.
Read the detailed description
Pheochromocytomas are tumors of chromaffin cells that synthesize catecholamines. This project tests the efficacy of radiotoxic treatment of malignant pheochromocytoma using (131)I-metaiodobenzylguanidine [(131)I-MIBG], and in particular, tests whether pre-treatment with enhancer pharmaceuticals increases the efficacy of experimental (131)I-MIBG treatment in reducing the size and number of tumors and the tumor burden.
- Conditions
- Pheochromocytoma
- Being tested
- [131]I-MIBG, 6-[18F]Fluorodopamine, [123]I-MIBG
- Keywords
- Cancer, Metastasis, Fluorodopamine, PET, Methylprednisolone, Catecholamines, Metanephrines, Alpha-Methyl-Para-Tyrosine, Retinoic Acid, Carbidopa
- Medical subject headings
- Pheochromocytoma, Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[131]I-MIBGDrug
6-[18F]FluorodopamineDrug
[123]I-MIBGDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Whether [(131)I]MIBG, given alone or in combination effectively treats malignant pheochromocytoma.
Measured: After injection and at 3, 24, 48 and 72 hours post-injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2001 (estimated)
- Study start5 Dec 2001
- Study completion8 Jan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PheochromocytomaStudies of the same condition, open and under way.
- 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
- Enrolment
- 32 participants
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00028106
- Sponsor's protocol ID
- 020032
- Other IDs
- 02-CH-0032
- Status last verified
- 21 Aug 2008
- First submitted
- 11 Dec 2001
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Schvartz C, Gibold C, Vuillemin B, Delisle MJ. Results of [131I]metaiodobenzylguanidine therapy administered to three patients with malignant pheochromocytoma. J Nucl Biol Med (1991). 1991 Oct-Dec;35(4):305-7.
PubMed 1823842Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R, Keiser HR. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern Med. 1988 Aug 15;109(4):267-73. doi: 10.7326/0003-4819-109-4-267.
PubMed 3395037Lumbroso J, Schlumberger M, Tenenbaum F, Aubert B, Travagli JP, Parmentier C. [131I]metaiodobenzylguanidine therapy in 20 patients with malignant pheochromocytoma. J Nucl Biol Med (1991). 1991 Oct-Dec;35(4):288-91.
PubMed 1823838
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (131)I-Metaiodobenzylguanidine Treatment of Malignant Pheochromocytoma
- ClinicalTrials.gov ID
- NCT00028106
- Acronym / sponsor ID
- 020032
- Conditions
- Pheochromocytoma
- Keywords
- Cancer, Metastasis, Fluorodopamine, PET, Methylprednisolone, Catecholamines, Metanephrines, Alpha-Methyl-Para-Tyrosine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 5 Dec 2001
- Study completion
- 8 Jan 2007
- First posted
- 12 Dec 2001 (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.
This study will evaluate the effectiveness of 131MIBG in treating malignant pheochromocytoma and whether sensitization medications improve the response to treatment. Pheochromocytoma is a rare type of tumor that usually occurs in the adrenal glands. The tumor cells release chemicals like adrenaline that can cause large increases in blood pressure and pulse rate, with serious health consequences. Tumor in the adrenal glands usually can be removed surgically, but if the pheochromocytoma is malignant-i.e., has spread to many sites in the body-or is located in places where surgery is difficult or impossible, no satisfactory treatment is available. 131MIBG is a combination of an adrenaline-like chemical and a radioactive form of iodine. The 131MIBG attaches to the tumor cells and the high concentration of radioactive iodine kills them. Previous studies using 131MIBG to treat pheochromocytoma had a 36% response rate in terms of complete or partial improvement. This study will examine whether adding other sensitization medications to the 131MIBG treatment regimen will enhance its effectiveness in reducing the size and number of tumors.
Patients 18 years of age and older with malignant or inoperable pheochromocytoma may be eligible for this 18-month study. Candidates will be screened with various tests and procedures, which may include a medical history, physical examination, blood and urine tests, lung function studies, electrocardiogram, echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and bone scans and other scans using radioactive MIBG and octreotide.
Participants will be randomly assigned to one of two treatment groups: 1) 131MIBG plus sensitization medications, or 2) 131MIBG alone. All patients will be hospitalized 3 to 5 days for each 131MIBG treatment. The drug will be infused through a vein (intravenously, or I.V.) over 10 to 30 minutes. Patients will receive up to 3 treatments, separated by at least 3 months. All patients will also take potassium to protect the thyroid gland from radioactive iodine generated by the 131MIBG. The potassium is taken twice a day for 30 days, beginning the day before the 131MIBG treatment. Patients in the sensitization group will receive the following additional drugs for sensitization: methylprednisolone, intravenously a few minutes before 131MIBG treatment; Roaccutan, by mouth (capsules) twice a day for 6 weeks before treatment; Demser, by mouth 3 times a week for 1 week before treatment, and Carbidopa, by mouth every 6 hours for 4 days before treatment.
After each treatment, patients will have a clinical evaluation and periodic blood tests to check for adverse side effects of radiotherapy. Follow-up visits at NIH will be scheduled at 12 and 18 months after the first 131MIBG treatment for clinical, laboratory and imaging tests. Patients who had tumors in the lungs before treatment will have lung function tests 1, 3, and 6 months after each treatment. CT, MRI 131MIBG, and PET scanning will be done 1 week before each treatment.
Patients who have tumors that have grown by more than 25% and none that have shrunk by more than 50% or who have developed one or more new tumors while on 131MIBG treatment will be taken off the study.
Detailed description
Pheochromocytomas are tumors of chromaffin cells that synthesize catecholamines. This project tests the efficacy of radiotoxic treatment of malignant pheochromocytoma using (131)I-metaiodobenzylguanidine [(131)I-MIBG], and in particular, tests whether pre-treatment with enhancer pharmaceuticals increases the efficacy of experimental (131)I-MIBG treatment in reducing the size and number of tumors and the tumor burden.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients will have malignant pheochromocytoma defined as a locally-invasive adrenal tumor and/or a metastatic extra-adrenal tumor located in tissues where chromaffin cells are not normally present.
- Histologic proof of pheochromocytoma is not required but the nature of the tumor will be confirmed either by surgical pathological diagnosis or by biochemical measurements.
- Patients may have single or multiple tumors. There must be at least one discrete metastatic tumor that can be detected and measured by CT or MRI. Metastatic tumor sites may or may not be resectable.
- The tumor(s) must concentrate [131]I-MIBG.
- Tumors may be stable, or be growing or increasing in number at the time of this study. There will be no limit on tumor size.
Key exclusion criteria (18 listed)
- Pregnant or lactating women will be excluded. A positive pregnancy test will exclude the patient from further participation in this protocol.
- Children (less than 18 years of age) and patients older than 70 years of age will be excluded.
- Impaired cardiovascular function (ejection fraction of less than 40%, symptomatic congestive heart failure, sustained blood pressure over 190/100, angina pectoris);
- Abnormal coagulation parameters (PT and PTT elevated by 30% above the normal);
- Hematocrit below 30%, hemoglobin below 10 g/dl, white blood cell count below 3000 per mm(3), absolute neutrophil count below 1000 per mm(3), platelet count below 100,000 per mm(3));
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 |
|---|---|---|
| [131]I-MIBG | Drug | – |
| 6-[18F]Fluorodopamine | Drug | – |
| [123]I-MIBG | Drug | – |
Primary outcome
Whether [(131)I]MIBG, given alone or in combination effectively treats malignant pheochromocytoma.
Time frame: After injection and at 3, 24, 48 and 72 hours post-injection
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 2 Jul 2017.
- Background: PubMed 1823842Schvartz C, Gibold C, Vuillemin B, Delisle MJ. Results of [131I]metaiodobenzylguanidine therapy administered to three patients with malignant pheochromocytoma. J Nucl Biol Med (1991). 1991 Oct-Dec;35(4):305-7.
- Background: PubMed 3395037Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R, Keiser HR. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern Med. 1988 Aug 15;109(4):267-73. doi: 10.7326/0003-4819-109-4-267.
- Background: PubMed 1823838Lumbroso J, Schlumberger M, Tenenbaum F, Aubert B, Travagli JP, Parmentier C. [131I]metaiodobenzylguanidine therapy in 20 patients with malignant pheochromocytoma. J Nucl Biol Med (1991). 1991 Oct-Dec;35(4):288-91.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 [131]I-MIBG, 6-[18F]Fluorodopamine and [123]I-MIBG in people with Pheochromocytoma, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 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 8 inclusion and 18 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 2 Jul 2017. 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?
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?
Whether [(131)I]MIBG, given alone or in combination effectively treats malignant pheochromocytoma. (time frame: After injection and at 3, 24, 48 and 72 hours post-injection). 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 NCT00028106, which also lists 3 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 2 Jul 2017.