Safety and Tolerability Profile of RAD001 Daily in Chinese Patients With Advanced Pulmonary Neuroendocrine Tumor

NCT01175096 | Unknown Phase 1 DMC

• 1 other identifier: CRAD001KCN01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Neuroendocrine Tumors; Carcinoid Tumor

Keywords

neuroendocrine tumors; carcinoid tumor; RAD001 (everolimus, Afinitor®)

Outcome Measures

Primary Outcomes (1)

• 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

  28 ±4 days

Secondary Outcomes (1)

• Tumor response

  6-week

Study Arms (1)

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.

Drug: RAD001 (everolimus, Afinitor®)

Interventions

RAD001 (everolimus, Afinitor®) DRUG

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.

Also known as: RAD001, everolimus, Afinitor®

RAD001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead
• Novartis: collaborator

Study Sites (1)

Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Carcinoid Tumor

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Yilong Wu, MD.PhD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 2, 2010
• First Posted: August 4, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: August 4, 2010

Record last verified: 2010-05

Locations

CN (1)