PheochromocytomaPhase 2PheoCarcRAD001NCT01152827
RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid
A Phase 2 study testing RAD001 in people with Pheochromocytoma and Extra-adrenal Paraganglioma, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
According to Martin F et al, AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors. In nonfunctioning carcinoid, the PI3K/AKT/mTOR pathway is activated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pheochromocytoma, Extra-adrenal Paraganglioma, Non-functioning Carcinoid
- What is being tested?
- RAD001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jul 2008to Dec 2011
- 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
- 1. Histologically or cytologically confirmed pheochromocytoma or extra-adrenal paraganglioma or carcinoid
- 2. Local, locally-advanced or metastatic disease documented as having shown progression on a scan (CT, MRI, MIBI scan) taken 2 to 12 months prior to baseline compared to a previous scan taken at any time in the past. Progression must be documented according to RECIST criteria.
- 3. Disease that is not amenable to surgery, radiation or combined modality therapy with curative intent.
- 4. Presence of at least one measurable target lesion for further evaluation according to RECIST criteria
- 5. 18 years or older
- 6. ECOG performance status 0, 1
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- 7. Previous treatment with chemotherapy, loco-regional therapy (e.g chemoembolization) are permitted providing that toxicity has resolved to ≤grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment.
- 8. Adequate organ function
- 9. A patient with the willingness to comply with the study protocol during the study period and capable of complying with it
- 10. A patient who signed the informed consent prior to the participation of the study and who understands that he/she has a right to withdrawal from participation in the study at any time without any disadvantages.
Who cannot join
- 1. A patient with no measurable disease
- 2. Prior chemotherapy, radiation therapy or surgery within 4 weeks prior to study entry except palliative radiotherapy to non-target lesions (within 2 weeks prior to study entry)
- 3. A patient with functioning carcinoid
- 4. A patient with previous active or passive immunotherapy
- 5. A patient with intestinal obstruction or impending obstruction, recent active upper GI bleeding
- 6. A pregnant or lactating patient
Show all 15Show fewer
- 7. A patient of childbearing potential without being tested for pregnancy at baseline or with being tested for positive. (A postmenopausal woman with the amenorrhea period of at least 12 months or longer is considered to have non-childbearing potential)
- 8. A man or woman of childbearing potential who has no willingness to use a contraceptive measure during the study
- 9. A patient with history of another malignant disease within past 5 years, except curatively treated basal cell carcinoma of skin and cervical carcinoma in situ.
- 10. A patient with history of uncontrolled seizures, central nervous system disorder or psychiatric disorders that are considered clinically significant by the investigator that would prohibit the understanding of informed consent or that may be considered to interfere with the compliance of the administration of the study medications.
- 11. A patient with clinically significant heart disease (e.g. congestive heart failure, symptomatic coronary artery diseases, cardiac arrhythmia, etc) or myocardial infarction within past 12 months.
- 12. Ongoing cardiac arrhythmia of grade ≥2, atrial fibrillation of any grade, or QTc interval>450msec for males or >470msec for female.
- 13. A patient with interstitial pneumonia or diffuse symptomatic fibrosis of the lungs
- 14. A patient with peripheral neuropathy of grade 1 by NCI CTC, caused by other factors (e.g. alcohol, diabetes, etc). If the absence of deep tendon reflexes is the only neurologic disorder, this condition does not apply to the exclusion criteria.
- 15. A patient with organ transplantation requiring immunosuppressive therapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of RAD001monotherapy in Patients With Unresectable Pheochromocytoma or Extra-adrenal Paraganglioma or Non-functioning Carcinoid
- According to Martin F et al, AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors.
- In nonfunctioning carcinoid, the PI3K/AKT/mTOR pathway is activated.
- Although mTOR is clearly an attractive therapeutic target in tumor, no clinical study on mTOR inhibition by RAD001 have been conducted in pheochromocytoma or extra-adrenal paraganglioma or non-functioning carcinoid.
- So we design this phase II study of RAD001 in pheochromocytoma or extra-adrenal paraganglioma or non-functioning carcinoid to evaluate the efficacy of RAD001 in this orphan disease.
Read the detailed description
Although several therapeutic options exist for patients with metastatic pheochromocytoma, all options are limited and there is no cure. Reduction of tumor size palliates symptoms, but a survival advantage of debulking is unproven. A reduced tumor burden can facilitate subsequent radiotherapy or chemotherapy. External-beam irradiation of bone metastases and radio frequency ablation of lesions are treatment alternatives. Chemotherapy with a combination of cyclophosphamide, vincristin, and dacarbazine can provide tumor regression and symptom relief in up to 50% of patients, but the responses are usually short-lived. To date, 131I-labeled MIBG therapy is the single most valuable adjunct to surgical treatment of malignant pheochromocytomas. As a single agent, 131I-labeled MIBG has a limited efficacy of cure, and there is no consensus on what doses to use for treating either bone or organ metastases. Multicenter studies are required to reach a consensus on the efficacy of high-dose versus fractionated medium doses of 131I-labeled MIBG and monotherapy versus combination therapy with other radio nuclides or modes of chemotherapy.
The PI3-K/Akt/mTOR pathway is dysregulated in many cancers and is activated by several upstream proteins, such as ras, TCL1, and bcr-abl, and membrane receptor tyrosine kinases, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor, c-kit, and Flt3. Increased expression and constitutive activation of the catalytic subunit of PI3-K and Akt and/or decreased or absent PTEN protein expression have been reported in many types of cancer. Activating mutation in PIK3CA, the gene for the catalytic subunit of PI3-K have been reported in 25% of gastric cancer.
Upstream in the growth-promoting pathways that converge on mTOR are critical molecules that are often deregulated in cancer. These deregulated molecules precede inappropriate signals that activate the mTOR switch, driving the growth and proliferation of the cancer cell. Because the number of potential defects that can cause inappropriate activation of mTOR is large and one or another is common to most cancer cells, blocking their effect at the point of convergence is a rational approach.
According to Martin F et al, AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors.
Although mTOR is clearly an attractive therapeutic target in tumor, no clinical study on mTOR inhibition by RAD001 have been conducted in pheochromocytoma or extra-adrenal paraganglioma.
So we conduct this phase II study of RAD001 in this disease And we also include the nonfunctioning carcinoid in this study.
- Being tested
- RAD001
- Keywords
- Pheochromocytoma, extra-adrenal paraganglioma, non-functioning carcinoid, RAD001
- Medical subject headings
- Pheochromocytoma, Paraganglioma, Extra-Adrenal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
RAD001 10 mg daily po medication.
Treatments will be continued until any of the following events occur
- progression of disease
- the subject develops unacceptable toxicity
- consent to participate in the study is withdrawn
| Study group | Role | What they receive |
|---|---|---|
| RAD001 | Experimental | RAD001 10 mg daily po medication Receives: Drug: RAD001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival rate at 4 months
proportion of patients who are alive and progression-free at the time of 4 months of treatment among all patients
Measured: 10 months
Secondary outcomes (4)
time to progression (TTP)
Measured: 10 months
overall survival (OS)
Measured: 2 years
response rate (RR)
Measured: 6 months
metabolic response rate by PET-CT
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2010 (estimated)
- Study startJul 2008
- Primary completionMay 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PheochromocytomaStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yung-Jue Bang, MD, PhD, Principal investigator, Seoul National University HospitalDo-Youn Oh, MD, PhD, Study director, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01152827
- Sponsor's protocol ID
- H-0710-049-223
- Acronym
- PheoCarcRAD001
- Status last verified
- Jun 2010
- First submitted
- 31 May 2010
- Last updated
- 20 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of RAD001monotherapy in Patients With Unresectable Pheochromocytoma or Extra-adrenal Paraganglioma or Non-functioning Carcinoid
- ClinicalTrials.gov ID
- NCT01152827
- Acronym / sponsor ID
- PheoCarcRAD001 / H-0710-049-223
- Keywords
- Pheochromocytoma, extra-adrenal paraganglioma, non-functioning carcinoid, RAD001
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- May 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 29 Jun 2010 (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.
- According to Martin F et al, AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors.
- In nonfunctioning carcinoid, the PI3K/AKT/mTOR pathway is activated.
- Although mTOR is clearly an attractive therapeutic target in tumor, no clinical study on mTOR inhibition by RAD001 have been conducted in pheochromocytoma or extra-adrenal paraganglioma or non-functioning carcinoid.
- So we design this phase II study of RAD001 in pheochromocytoma or extra-adrenal paraganglioma or non-functioning carcinoid to evaluate the efficacy of RAD001 in this orphan disease.
Detailed description
Although several therapeutic options exist for patients with metastatic pheochromocytoma, all options are limited and there is no cure. Reduction of tumor size palliates symptoms, but a survival advantage of debulking is unproven. A reduced tumor burden can facilitate subsequent radiotherapy or chemotherapy. External-beam irradiation of bone metastases and radio frequency ablation of lesions are treatment alternatives. Chemotherapy with a combination of cyclophosphamide, vincristin, and dacarbazine can provide tumor regression and symptom relief in up to 50% of patients, but the responses are usually short-lived. To date, 131I-labeled MIBG therapy is the single most valuable adjunct to surgical treatment of malignant pheochromocytomas. As a single agent, 131I-labeled MIBG has a limited efficacy of cure, and there is no consensus on what doses to use for treating either bone or organ metastases. Multicenter studies are required to reach a consensus on the efficacy of high-dose versus fractionated medium doses of 131I-labeled MIBG and monotherapy versus combination therapy with other radio nuclides or modes of chemotherapy.
The PI3-K/Akt/mTOR pathway is dysregulated in many cancers and is activated by several upstream proteins, such as ras, TCL1, and bcr-abl, and membrane receptor tyrosine kinases, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor, c-kit, and Flt3. Increased expression and constitutive activation of the catalytic subunit of PI3-K and Akt and/or decreased or absent PTEN protein expression have been reported in many types of cancer. Activating mutation in PIK3CA, the gene for the catalytic subunit of PI3-K have been reported in 25% of gastric cancer.
Upstream in the growth-promoting pathways that converge on mTOR are critical molecules that are often deregulated in cancer. These deregulated molecules precede inappropriate signals that activate the mTOR switch, driving the growth and proliferation of the cancer cell. Because the number of potential defects that can cause inappropriate activation of mTOR is large and one or another is common to most cancer cells, blocking their effect at the point of convergence is a rational approach.
According to Martin F et al, AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors.
Although mTOR is clearly an attractive therapeutic target in tumor, no clinical study on mTOR inhibition by RAD001 have been conducted in pheochromocytoma or extra-adrenal paraganglioma.
So we conduct this phase II study of RAD001 in this disease And we also include the nonfunctioning carcinoid in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 | Experimental | Drug: RAD001RAD001 10 mg daily po medication |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 1. Histologically or cytologically confirmed pheochromocytoma or extra-adrenal paraganglioma or carcinoid
- 2. Local, locally-advanced or metastatic disease documented as having shown progression on a scan (CT, MRI, MIBI scan) taken 2 to 12 months prior to baseline compared to a previous scan taken at any time in the past. Progression must be documented according to RECIST criteria.
- 3. Disease that is not amenable to surgery, radiation or combined modality therapy with curative intent.
- 4. Presence of at least one measurable target lesion for further evaluation according to RECIST criteria
- 5. 18 years or older
Key exclusion criteria (15 listed)
- 1. A patient with no measurable disease
- 2. Prior chemotherapy, radiation therapy or surgery within 4 weeks prior to study entry except palliative radiotherapy to non-target lesions (within 2 weeks prior to study entry)
- 3. A patient with functioning carcinoid
- 4. A patient with previous active or passive immunotherapy
- 5. A patient with intestinal obstruction or impending obstruction, recent active upper GI bleeding
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 |
|---|---|---|
| RAD001RAD001 10 mg daily po medication. Treatments will be continued until any of the following events occur * progression of disease * the subject develops unacceptable toxicity * consent to participate in the study is withdrawn | Drug | RAD001 |
Primary outcome
progression-free survival rate at 4 months
Time frame: 10 months
proportion of patients who are alive and progression-free at the time of 4 months of treatment among all patients
4 secondary outcomes
time to progression (TTP)
Time frame: 10 months
overall survival (OS)
Time frame: 2 years
response rate (RR)
Time frame: 6 months
metabolic response rate by PET-CT
Time frame: 2 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 20 May 2015.
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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.
Yung-Jue Bang, MD, PhD principal investigator
Seoul National University Hospital
Do-Youn Oh, MD, PhD study director
Seoul National University Hospital
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 RAD001 in people with Pheochromocytoma and Extra-adrenal Paraganglioma, run by Seoul National University Hospital at 1 site in South Korea.
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 10 inclusion and 15 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 May 2015. 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 South Korea. 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?
progression-free survival rate at 4 months (time frame: 10 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 May 2015; AzTrials last refreshed its copy on 31 Oct 2026.