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Phase II Trial of REVLIMID® (Lenalidomide) for Therapy of Radioiodine-Unresponsive Papillary & Follicular Thyroid Carcinomas

Phase 2
18 Years
Open (Enrolling)
Thyroid Neoplasms

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Trial Information

Phase II Trial of REVLIMID® (Lenalidomide) for Therapy of Radioiodine-Unresponsive Papillary & Follicular Thyroid Carcinomas

Thalidomide has found new uses as a tumor anti-angiogenesis agent that is capable of
diminishing the proliferation of angiogenesis-dependent solid malignancies. Distantly
metastatic, unresectable medullary thyroid carcinomas, as well as de-differentiated
papillary and follicular thyroid carcinomas, which no longer concentrate radioiodine, have
no known effective systemic therapies. We have verified, in the context of a completed phase
2 clinical trial, that thalidomide has significant activity in thyroid carcinomas that are
no longer radioiodine avid and are rapidly progressive. This activity has only limited
durability of around 7 months and is associated with significant toxicities of sedation,
constipation and neuropathy.

REVLIMID® (lenalidomide) is an analog of thalidomide with the chemical name,
alpha-(3-aminophthalimido) glutarimide. REVLIMID® is noted to be more potent than
thalidomide in inhibiting the production of TNF-alpha. It has more than doubled the
inhibition of microvessel growth at the same concentration as thalidomide in a rat aorta
angiogenesis model as well as greatly enhanced activity as an IMiD. Most importantly, it
lacks much of the toxicity of thalidomide, particularly in regards to somnolence,
neuropathy, or biochemical effects. In fact, patients with multiple myeloma, known to be
resistant to thalidomide, were still seen to exhibit clinical responses to REVLIMID®. This
makes REVLIMID® an appropriate agent to investigate in a phase 2 trial in thyroid carcinoma.

Inclusion Criteria:

- Histological confirmation of follicular, papillary, insular, or Hürthle-cell thyroid
carcinoma. Histologic slides and/or tissue blocks must be reviewed at the University
of Kentucky Medical Center.

- Patients must have an unresectable, distantly metastatic tumor, which does not
concentrate radioactive iodine. Alternatively, follicular or papillary thyroid
carcinoma patients with large distant tumor burdens which have not sufficiently
responded to more than 800 mCi I-131 cumulative therapy and are progressive (criteria
#4) may be appropriate for inclusion.

- No systemic chemotherapy agents within 4 weeks of initiation of therapy.

- Patients must have 3 consecutive radiographic evaluations demonstrating a cumulative
30% increase in tumor volume over a period of one year or less.

- Patients must be over the age of 18 years with the ability to understand and willing
to sign an informed consent.

- Non-pregnant (if female). Women of childbearing potential (fertile females) must have
a negative serum or urine pregnancy test within one day of starting study drug. In
addition, sexually active fertile female subjects must agree to adequate
contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal
ligation, intrauterine device, barrier contraceptive with spermicide; or vasectomized
partner) while on study drug. Men must agree to use latex condoms when having sex
with fertile women.

- Karnofsky performance status ≥ 70.

- Baseline laboratory studies:

- absolute neutrophil count (ANC) > 1000/mm3

- platelet count ≥ 100 K/mm3

- creatinine ≤ 1.5 mg/dL, and

- transaminase levels (AST/SGOT, ALT/SGPT) ≤ 2 x upper limit of normal (ULN) (or ≤
5 x I:M if hepatic metastases are present)

- Disease free of other prior malignancies for ≥ 5 years, with the exception of
currently treated basal cell/squamous cell carcinoma of the skin or "in-situ"
carcinoma of the cervix or breast.

- Thyroid stimulating hormone (TSH, thyrotropin) levels must be suppressed with
sufficient levothyroxine to be kept beneath the normal range of the assay.

Exclusion Criteria:

- Patients may not have had prior REVLIMID® therapy.

- No serious concomitant medical or psychiatric illness that might interfere with
informed consent or conduct of the study, including active infections that are not
controlled with medication.

- Patients must not be pregnant or breastfeeding.

- Use of any other experimental drug or therapy within 28 days of baseline.

- Known hypersensitivity to thalidomide.

- The development of erythema nodosum, characterized by a desquamating rash, while
taking thalidomide or similar drugs.

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.

- Concurrent use of other anti-cancer agents or treatments, with the exception of
thyrotropin-suppression by levothyroxine.

- All subjects with central nervous system involvement, with the exception of those
subjects whose central nervous system metastases have been treated with either
radiotherapy and/or surgery and remain asymptomatic with no evidence of active
central nervous system disease (verified by computed tomography [CT] scan or magnetic
resonance imaging [MRI]) for at least 6 months.

- Known to be positive for HIV or infectious hepatitis, type A, B, or C.

- Patients with medullary or anaplastic thyroid carcinomas are excluded. Patients
whose disease is limited to bone metastases are excluded.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor response

Outcome Time Frame:

See protocol

Safety Issue:


Principal Investigator

Kenneth B Ain, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Kentucky


United States: Food and Drug Administration

Study ID:




Start Date:

February 2006

Completion Date:

Related Keywords:

  • Thyroid Neoplasms
  • Lenalidomide
  • Clinical Trials phase II
  • Carcinomas, thyroid
  • Radioiodine-Unresponsive Papillary & Follicular Thyroid Carcinomas
  • Neoplasms
  • Carcinoma
  • Thyroid Neoplasms
  • Thyroid Diseases
  • Adenocarcinoma, Follicular



University of Kentucky Markey Cancer Center Lexington, Kentucky  40536