RAD001 for Patients With Radioiodine Refractory Thyroid Cancer

NCT00936858 | Completed Phase 2 Results DMC

• 1 other identifier: 09-049
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief Summary

Since thyroid cancer becomes refractory to radioactive iodine, treatment options are very limited. Tyrosine kinase inhibitors such as sorafenib have recently shown promise. This trial seeks to expand treatment options for this disease with a new, oral drug called RAD001. It is an inhibitor of the mTOR pathway and has shown activity in neuroendocrine cancers of the gastrointestinal tract and has been approved for the treatment of metastatic renal cell cancer.

Conditions

Thyroid Cancer

Keywords

radioiodine refractory thyroid cancer; RAD001

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival

  Progression free survival (PFS) is defined as the time from start of treatment to disease progression or death from any cause as estimated by Kaplan Meier methods. Progression is measured using RECIST 1.1 criteria, defined as at least a 20% increase in size in target lesion and/or unequivocal progression of non-target lesions and/or appearance of new lesions. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free.

  Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 48 months.

Secondary Outcomes (3)

• Objective Response Rate

  Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 48 months.

• Median Overall Survival

  Every 2 months for first 24 months, then every 3 months from >24 to 60 months; up to 5 years post study registration.

• Mean Change in Quality of Life [Medullary Thyroid Cancer Population Only]

  Measured at baseline and then again at cycle 8 (8 months).

Study Arms (1)

Arm A

EXPERIMENTAL

RAD001 will be administered orally as once daily dose of 10 mg (one 10mg tablet or two 5mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity.

Drug: RAD001

Interventions

RAD001 DRUG

Also known as: Afinitor (everolimus)

Arm A

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed locally advanced or metastatic thyroid cancer, excluding thyroid lymphomas not amenable to or refractory to surgical resection, external beam radiotherapy, radioiodine or other local therapies.
• Prior therapy with chemotherapy and targeted therapies except for mTor inhibitors is allowed.
• Medullary thyroid cancer with documented evidence of disease progression by modified RECIST within 6 months before study day 1 or symptomatic disease at the time of screening in the absence of documented disease progression.
• Differentiated thyroid cancer with documented evidence of disease progression by modified RECIST within 6 months before study day 1.
• Anaplastic thyroid cancer with disease progression with documented disease progression by modified RECIST within 6 months of study day 1.
• Patients must have at least one measurable site of disease according to RECIST criteria that has not previously irradiated. If the patient has has previous radiation to the marker lesion(s), there must be evidence of progression since radiation.
• years of age or older
• WHO performance status 2 or less
• Adequate bone marrow, liver, and renal function
• Fasting serum cholesterol 300mg/dL or less OR 7.75 mmol/L or less AND fasting triglycerides 2.5x ULN or less

You may not qualify if:

• Patients receiving anticancer therapies within last 2 weeks or who have received radiation therapy within 3 weeks of study day 1
• Prior therapy with mTOR inhibitors
• Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study
• Prior treatment with any investigational drug within the preceding 3 weeks
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within 2 weeks of study entry or during study period
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• A known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
• Patients with an active, bleeding diathesis
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods
• Patients who have received prior treatment wih an mTOR inhibitor
• Patients with a known hypersensitivity to RAD001 or other rapamycins or to its excipients

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Massachusetts General Hospital: collaborator
• M.D. Anderson Cancer Center: collaborator
• MOUNT SINAI HOSPITAL: collaborator
• Novartis: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Glenn Hanna
• Organization: Dana-Farber Cancer Institute

glenn_hanna@dfci.harvard.edu

6176323090

Study Officials

• Glenn Hanna, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 10, 2009
• Study Start: July 1, 2009
• Primary Completion: February 27, 2020
• Study Completion: February 27, 2020
• Last Updated: October 22, 2021
• Results First Posted: September 28, 2021

Record last verified: 2021-10

Locations

US (4)