Neoplasms

Gland and Hormone Related Diseases

All Conditions

Thyroid Neoplasms

Thyroid Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

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.

RAD001

Glenn Hanna, MD

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.

* RAD001 will be taken once a day in the morning starting on Day 1 and continue until the participant is no longer participating in the study treatment.
* A history and physical exam will be performed the first day of the study and then once a month. Blood tests including coagulation studies, and thyroid studies will be performed monthly. A urine sample will need to be provided on the first day of treatment and then every 2 months. Imaging consisting of a CT or MRI of the neck, chest and abdomen will be done every 8 weeks after starting RAD001.
* Participants will remain on this research study for up to 24 months. However, if the participants doctor feels that they are benefiting from the study drug and they do not have severe side effects, they may be given the option to continue taking RAD001.

RAD001 for Patients With Radioiodine Refractory Thyroid Cancer

A Phase II Trial Using RAD001 for Patients With Radioiodine Refractory Thyroid Cancer

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.

The objective response rate is the proportion of participants achieving complete response (CR) or partial response (PR) on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria.

PR or better is achieved if the following are true:

Target Lesions:

-At least a 30% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Non-target Lesions:

No progression. No appearance new lesions or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Bone Lesions:

-\>50% increase in lesions.

-No new lesions.

Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.

The M. D. Anderson Symptom Inventory (MDASI) questionnaire was used to assess quality of life. Questions 1 to 19 were scored. Each of the 19 questions have a response range of 0 - 10, where 0 represents "not present" and 10 represents "as bad as you can imagine". The 19 responses are averaged together to create a mean score, with a lower score indicating a better quality of life. All questionnaire mean scores at each timepoint are averaged together to give a mean score at that timepoint (baseline and week 8) The mean change in quality of life is calculated by subtracting the baseline mean score from the week 8 mean score.

Massachusetts General Hospital

M.D. Anderson Cancer Center

MOUNT SINAI HOSPITAL

Novartis

Dana-Farber Cancer Institute

Principal Investigator

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.

RAD001: Taken orally once a day in the morning

Arm A

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Subtype

Tyrosine Kinase Inhibitors

Surgery

Radioactive Iodine

External Beam Radiotherapy

Previous Therapies

ECOG Performance Status

None

Bone

Lung

Liver

Lymph Nodes

Other

Site of Distant Metastasis

Dr. Glenn Hanna

We will declare the trial a success after observing 7 or more patients with PFS within 6 months. The study will have alpha = 0.092 and power =0.970, assuming a 6 month PFS probability of 0.12 for the null and a PFS probability of 0.35 as the alternative hypothesis.

Median Progression Free Survival

Objective Response Rate

Median Overall Survival

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.

RAD001

Only 8 of the 10 participants with Medullary Thyroid Cancer filled out both questionnaires (one at baseline and one at cycle 8).

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

RAD001 Group

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
RAD001 for Patients With Radioiodine Refractory Thyroid Cancer	NCT00936858	Thyroid Cancer	RAD001	18 Years -	Dana-Farber Cancer Institute
RAD001 for Patients With Radioiodine Refractory Thyroid Cancer	NCT00936858	Thyroid Cancer	RAD001	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for radioiodine refractory thyroid cancer