Neuroendocrine TumorsPhase 1/2NCT01175096
Safety and Tolerability Profile of RAD001 Daily in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor
A Phase 1/2 study testing RAD001 (everolimus, Afinitor®) in people with Neuroendocrine Tumors and Carcinoid Tumor, run by Guangdong Provincial People's Hospital at 1 site in China.
Trial summary
RAD001 continues to be investigated as an anticancer agent on new indications such as neuroendocrine tumors (incl. carcinoid), breast cancer, liver cancer, gastric cancer and lymphoma based on its potential to act: directly on the tumor cells by inhibiting tumor cell growth and proliferation indirectly by inhibiting… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors, Carcinoid Tumor
- What is being tested?
- RAD001 (everolimus, Afinitor®)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Jul 2010to Jan 2012
- Phase
- Phase 1/2
- 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
- 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
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- 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
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
1 site in 1 country.
China1 site
Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences
Guangzhou, Guangdong, 510080
About this study
Official title: A Phase Ib, Open-label Study to Evaluate RAD001 as Monotherapy Treatment in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor
RAD001 continues to be investigated as an anticancer agent on new indications such as neuroendocrine tumors (incl. carcinoid), breast cancer, liver cancer, gastric cancer and lymphoma based on its potential to act:
- directly on the tumor cells by inhibiting tumor cell growth and proliferation
- indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity and VEGF production and VEGF-induced proliferation of endothelial cells)
Read more
A role for RAD001 in combination with Sandostatin LAR® Depot in the treatment of advanced carcinoid tumor is suggested by data on the regulatory role of mTOR in cell growth and protein translation and the finding that somatostatin-induced growth arrest is mediated in part by inhibition of the PI3K pathway (Charland, et al. 2001).
The present study is designed to collect safety/tolerability data and evidences for efficacy of RAD001 in the medically highly unmet indication of advanced pulmonary neuroendocrine tumor in Chinese patients.
Read the detailed description
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.
- Conditions
- Neuroendocrine Tumors, Carcinoid Tumor
- Being tested
- RAD001 (everolimus, Afinitor®)
- Keywords
- neuroendocrine tumors, carcinoid tumor, RAD001 (everolimus, Afinitor®)
- Medical subject headings
- Neuroendocrine Tumors, Carcinoid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001 (everolimus, Afinitor®)Drug
Also called RAD001, everolimus, Afinitor®
RAD001 will be provided by Novartis to the study sites. RAD001 is formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 30 tablets. The study site will dispense an adequate supply of RAD001 to the patient for self-administration at home.
2 x 5 mg (=10 mg) RAD001 p.o., once daily, at the same time each day, One treatment cycle consists of 28 days.
| Study group | Role | What they receive |
|---|---|---|
| RAD001 | Active comparator | 2 x 5 mg (=10 mg) RAD001 p.o., once daily, at the same time each day Dose level modifications/interruptions must follow guidelines. One treatment cycle consists of 28 days. Receives: Drug: RAD001 (everolimus, Afinitor®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
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
Measured: 28 ±4 days
Secondary outcomes (1)
Tumor response
Tumor response will be evaluated at the end of every 6-week treatment period, Treatment will continue until tumor progression as judged by the local investigator using the RECIST criteria, unacceptable toxicity, death, or discontinuation from the study for any other reason.
Measured: 6-week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionJan 2012 (estimated)
- Study completionJan 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by Guangdong Provincial People's 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Investigators
- Yilong Wu, MD.PhD, Principal investigator, Guangdong Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01175096
- Sponsor's protocol ID
- CRAD001KCN01
- Status last verified
- May 2010
- First submitted
- 2 Aug 2010
- Last updated
- 4 Aug 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open-label Study to Evaluate RAD001 as Monotherapy Treatment in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor
- ClinicalTrials.gov ID
- NCT01175096
- Acronym / sponsor ID
- CRAD001KCN01
- Conditions
- Neuroendocrine Tumors, Carcinoid Tumor
- Keywords
- neuroendocrine tumors, carcinoid tumor, RAD001 (everolimus, Afinitor®)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Guangdong Provincial People's HospitalUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jul 2010
- Primary completion
- Jan 2012 (estimated)
- Study completion
- Jan 2012 (estimated)
- First posted
- 4 Aug 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.
RAD001 continues to be investigated as an anticancer agent on new indications such as neuroendocrine tumors (incl. carcinoid), breast cancer, liver cancer, gastric cancer and lymphoma based on its potential to act:
- directly on the tumor cells by inhibiting tumor cell growth and proliferation
- indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell HIF-1 activity and VEGF production and VEGF-induced proliferation of endothelial cells)
A role for RAD001 in combination with Sandostatin LAR® Depot in the treatment of advanced carcinoid tumor is suggested by data on the regulatory role of mTOR in cell growth and protein translation and the finding that somatostatin-induced growth arrest is mediated in part by inhibition of the PI3K pathway (Charland, et al. 2001).
The present study is designed to collect safety/tolerability data and evidences for efficacy of RAD001 in the medically highly unmet indication of advanced pulmonary neuroendocrine tumor in Chinese patients.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 | Active comparator | Drug: RAD001 (everolimus, Afinitor®)2 x 5 mg (=10 mg) RAD001 p.o., once daily, at the same time each day Dose level modifications/interruptions must follow guidelines. One treatment cycle consists of 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed carcinoid tumors
- Newly diagnosed advanced carcinoid tumors
- Measurable tumors
- Chinese men and women, age ≥ 18 years
- ECOG performance status ≤ 2
Key exclusion criteria (25 listed)
- 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
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 |
|---|---|---|
| RAD001 (everolimus, Afinitor®)Also: RAD001, everolimus, Afinitor®RAD001 will be provided by Novartis to the study sites. RAD001 is formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 30 tablets. The study site will dispense an adequate supply of RAD001 to the patient for self-administration at home. 2 x 5 mg (=10 mg) RAD001 p.o., once daily, at the same time each day, One treatment cycle consists of 28 days. | Drug | RAD001 |
Primary outcome
Safety and tolerability
Time frame: 28 ±4 days
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
1 secondary outcome
Tumor response
Time frame: 6-week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2010.
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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.
Yilong Wu, MD.PhD principal investigator
Guangdong Provincial People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RAD001 (everolimus, Afinitor®) in people with Neuroendocrine Tumors and Carcinoid Tumor, run by Guangdong Provincial People's Hospital at 1 site in China.
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 12 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 4 Aug 2010. 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 China. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
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?
Safety and tolerability (time frame: 28 ±4 days). 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 4 Aug 2010.