RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid (PheoCarcRAD001)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by Seoul National University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01152827
First received: May 31, 2010
Last updated: June 28, 2010
Last verified: June 2010
  Purpose
  • 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.

Condition Intervention Phase
Pheochromocytoma
Extra-Adrenal Paraganglioma
Non-functioning Carcinoid
Drug: RAD001
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of RAD001monotherapy in Patients With Unresectable Pheochromocytoma or Extra-adrenal Paraganglioma or Non-functioning Carcinoid

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • progression-free survival rate at 4 months [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    proportion of patients who are alive and progression-free at the time of 4 months of treatment among all patients


Secondary Outcome Measures:
  • time to progression (TTP) [ Time Frame: 10 months ] [ Designated as safety issue: No ]
  • overall survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • response rate (RR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • metabolic response rate by PET-CT [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: July 2008
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001
RAD001 10 mg daily po medication
Drug: RAD001

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01152827

Contacts
Contact: Yung-Jue Bang, MD, PhD 82-2-2072-2390 bangyj@snu.ac.kr
Contact: Do-Youn Oh, MD, PhD 82-2-2072-0701 ohdoyoun@snu.ac.kr

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Yung-Jue Bang, MD, PhD    82-2-2072-2390    bangyj@snu.ac.kr   
Contact: Do-Youn Oh, MD, PhD    82-2-2072-0701    ohdoyoun@snu.ac.kr   
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Yung-Jue Bang, MD, PhD Seoul National University Hospital
Study Director: Do-Youn Oh, MD, PhD Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Yung-Jue Bang/Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01152827     History of Changes
Other Study ID Numbers: H-0710-049-223
Study First Received: May 31, 2010
Last Updated: June 28, 2010
Health Authority: Korea, Republic of :Food and Drug Administration

Keywords provided by Seoul National University Hospital:
Pheochromocytoma
extra-adrenal paraganglioma
non-functioning carcinoid
RAD001

Additional relevant MeSH terms:
Paraganglioma
Paraganglioma, Extra-Adrenal
Carcinoid Tumor
Pheochromocytoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 20, 2014