A Phase Ib, Open-label Study to Evaluate RAD001 as Monotherapy Treatment in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor
18 Years
N/A
Both
Neuroendocrine Tumors, Carcinoid Tumor
Trial Information
A Phase Ib, Open-label Study to Evaluate RAD001 as Monotherapy Treatment in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor
The purpose of this phase I b study is to characterize the safety, tolerability, and
efficacy of 10 mg RAD001 administered orally on a continuous once-daily dosing regimen in
the treatment of advanced pulmonary neuroendocrine tumor. The neuroendocrine tumors arising
from bronchi and lung account for 30% of all carcinoid tumors, and there are a lot of well
differentiated adenocarcinoma, squamous cancer and large cell lung cancer with significant
neuroendocrine carcinoma characteristics who seems had a similarly prognosis with carcinoid
tumor. There is no effective treatment available for advanced pulmonary NETs at this time.
The rationale for this study is based on both preclinical and clinical considerations. IGF-1
is a known autocrine regulator of CgA secretion and cell growth in human neuroendocrine
tumor cells (von Wichert, et al. 2000; Wulbrand, et al. 2000; Van Gompel and Chen 2004). A
role for RAD001 as monotherapy in carcinoid and pancreatic NET is suggested by the
regulatory role of mTOR in cell growth, metabolism and protein translation (Fingar and
Blenis 2004; Vignot, et al. 2005) and the Novartis observation that the PI3K/mTOR pathway is
activated by IGF-1 in carcinoid and pancreatic NET cells (von Wichert, et al. 2000; Van
Gompel and Chen 2004).
The proposed RAD001 dosage regimen is 10 mg/day in both monotherapy and combination therapy
settings. This regimen is based both on Novartis Phase I/II studies and on results from an
investigator-sponsored study in NET. Initial Phase I studies of the RAD001 10 mg/day
schedule demonstrated dose limiting toxicities in 2 of 12 patients. Tolerability of this
schedule was verified in a total of 33 patients in Phase 1 studies as well as in 12 breast
cancer patients treated with letrozole 2.5 mg plus RAD001 10 mg/day. Pharmacodynamic
modeling indicates that downstream effectors of mTOR are completely suppressed by RAD001 at
the 10 mg/day dose. No increased toxicity is expected from use of RAD001 in combination with
Sandostatin LAR® Depot. The investigator-sponsored study in NET, toxicity observed with
RAD001 5 mg/day in combination with Sandostatin LAR® Depot was similar to that observed for
RAD001 5 mg/day alone in Phase 1 studies (Yao, et al. 2006). Therefore a dose of RAD001 10
mg/day will be evaluated in this study.
For carcinoid tumor
Inclusion Criteria:
- Histologically confirmed carcinoid tumors
- Newly diagnosed advanced carcinoid tumors
- Measurable tumors
- Chinese men and women, age ≥ 18 years
- ECOG performance status ≤ 2
- Written informed consent obtained
Exclusion Criteria:
- Patients with either clinically apparent central nervous system metastases or
carcinomatous meningitis(non-clinical symptoms with brain lesions is eligible)
- Received Cytotoxic chemotherapy, immunotherapy or radiotherapy prior to enrollment
- Patients with a concurrent malignancy, or history of prior malignancy within the past
three years, except for basal cell or squamous cell skin cancer, carcinoma in situ of
the cervix, treated early stage (T1a) prostate cancer or treated early stage (DCIS or
LCIS) breast cancer
- Prior therapy with RAD001 or other mTOR inhibitors (sirolimus, temsirolimus,
everolimus)
- Major surgery in the past two weeks
- Any medical condition resulting in >CTC grade 2 dyspnea
- Patients with recent hemoptysis associated with carcinoid tumor (> 1 teaspoon in a
single episode within 4 weeks)
- Serious, severe or uncontrolled medical or psychiatric condition
- Patients receiving chronic treatment with corticosteroids or another
immunosuppressive agent
- Patients with a known history of HIV seropositivity
- Women of childbearing potential must have had a negative serum pregnancy test within
3 days prior to the administration of RAD001
- Patients who have received an investigative drug or therapy within the last 30 days
For adenocarcinoma and Large cell lung cancer with significant neuroendocrine carcinoma
characteristics
Inclusion Criteria:
- Histologically confirmed locally unresectable or advanced well differentiated
（adenocarcinoma,squamous cancer and large cell lung cancer ）with significant
neuroendocrine carcinoma characteristics tumors : CgA and/or Synaptophysin +(at
least 10% of cells that would have to be positive ).( the pathology shows a
neuroendocrine component histologically should be at least 10% of tissue within the
specimen that is read as "neuroendocrine component").
- Measurable tumors
- Patients with newly diagnosed advanced cancer or progressed after 1st line treatment
is eligible
- Chinese men and women, age ≥ 18 years
- ECOG performance status ≤ 2
- Written informed consent obtained
Exclusion Criteria:
- Patients with either clinically apparent central nervous system metastases or
carcinomatous meningitis(non-clinical symptoms with brain lesions is eligible)
- Radiotherapy to primary tumor in lung lesions prior to enrollment
- Patients with a concurrent malignancy, or history of prior malignancy within the past
three years, except for basal cell or squamous cell skin cancer, carcinoma in situ of
the cervix, treated early stage (T1a) prostate cancer or treated early stage (DCIS or
LCIS) breast cancer
- Prior therapy with RAD001 or other mTOR inhibitors (sirolimus, temsirolimus,
everolimus)
- Major surgery in the past two weeks
- Any medical condition resulting in > CTC grade 2 dyspnea
- Patients with recent hemoptysis associated with carcinoid tumor (> 1 teaspoon in a
single episode within 4 weeks)
- Serious, severe or uncontrolled medical or psychiatric condition
- Patients receiving chronic treatment with corticosteroids or another
immunosuppressive agent
- Patients with a known history of HIV seropositivity
- Women of childbearing potential must have had a negative serum pregnancy test within
3 days prior to the administration of RAD001
- Patients who have received an investigative drug or therapy within the last 30 days
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety and tolerability
Outcome Description:
Safety assessments will consist of monitoring and recording all adverse events, including serious adverse events, the regular monitoring of hematology and blood chemistry, regular monitoring of vital signs and physical condition. A safety visit will take place on day 28 (±4 days) following the last dose of study drug administered. Patients will be asked to visit the clinic on day 1 of every 6 weeks for safety assessments. Safety and tolerability will be assessed according to the NIH/NCI CTC
Outcome Time Frame:
28 ±4 days
Safety Issue:
Yes
Principal Investigator
Yilong Wu, MD.PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Guangdong General Hospital
Authority:
China: Food and Drug Administration
Study ID:
CRAD001KCN01
NCT ID:
NCT01175096
Start Date:
July 2010
Completion Date:
January 2012
Related Keywords:
- Neuroendocrine Tumors
- Carcinoid Tumor
- neuroendocrine tumors
- carcinoid tumor
- RAD001 (everolimus, Afinitor®)
- Carcinoid Tumor
- Neuroendocrine Tumors
Name | Location |
|---|
