REVLIMID® (Lenalidomide) for Therapy of Radioiodine-Unresponsive Papillary and Follicular Thyroid Carcinomas

• Sponsor: Kenneth Ain (Other)
• Overall Status: Completed
• CT.gov ID: NCT00287287
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 25
• Location: 1
• Arm: 1
• Actual Duration (Months): 53.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the anti-tumor activity of REVLIMID® (lenalidomide), administered as a single agent, in patients with distantly metastatic thyroid carcinomas which are unresponsive to systemic radioiodine, in terms of tumor response and response duration.

Condition or Disease	Intervention/Treatment	Phase
Thyroid Neoplasms	Drug: Lenalidomide	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of REVLIMID® (Lenalidomide) for Therapy of Radioiodine-Unresponsive Papillary & Follicular Thyroid Carcinomas
• Actual Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Jul 6, 2010
• Actual Study Completion Date: Jul 6, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide (Revlimid) Treatment will be initated at 25 mg/day taken in the morning. Dose adjustments may be made to alleviate toxicities.	Drug: Lenalidomide; Initial dose is 25 mg/day dose will be adjusted accordingly as needed. Dose range for the study is 5 to 25 mg/day; Other Names: Revlimid

Outcome Measures

Primary Outcome Measures

1. Response Rate [4 years]

   Percentage of patients who responded to treatment (either stable disease or complete response) based on total tumor volume measurements from CT scans.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kentucky Markey Cancer Center	Lexington	Kentucky	United States	40536

Sponsors and Collaborators

• Kenneth Ain
• Celgene Corporation

Investigators

• Principal Investigator: Kenneth B Ain, M.D., University of Kentucky

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 21, 2008

More Information

Publications

None provided.

• Responsible Party: Kenneth Ain, Principal Investigator, University of Kentucky
• ClinicalTrials.gov Identifier: NCT00287287
• Other Study ID Numbers: 05-701-F3R; NCT00381498
• First Posted: Feb 6, 2006
• Last Update Posted: Jun 12, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Kenneth Ain, Principal Investigator, University of Kentucky: Lenalidomide; Clinical Trials phase II; Carcinomas, thyroid; Radioiodine-Unresponsive; Papillary; Follicular
• Additional relevant MeSH terms: Carcinoma; Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Diseases; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Lenalidomide (Revlimid)
Arm/Group Description	Treatment will be initated at 25 mg/day taken in the morning. Dose adjustments may be made to alleviate toxicities. Lenalidomide: Initial dose is 25 mg/day dose will be adjusted accordingly as needed. Dose range for the study is 5 to 25 mg/day
Period Title: Overall Study
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Lenalidomide (Revlimid)
Arm/Group Description	Treatment will be initated at 25 mg/day taken in the morning. Dose adjustments may be made to alleviate toxicities. Lenalidomide: Initial dose is 25 mg/day dose will be adjusted accordingly as needed. Dose range for the study is 5 to 25 mg/day
Overall Participants	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (10.5)
Sex: Female, Male (Count of Participants)
Female	11 44%
Male	14 56%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	25 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	23 92%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Percentage of patients who responded to treatment (either stable disease or complete response) based on total tumor volume measurements from CT scans.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide (Revlimid)
Arm/Group Description	Treatment will be initated at 25 mg/day taken in the morning. Dose adjustments may be made to alleviate toxicities.
Measure Participants	25
Count of Participants [Participants]	17 68%

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	Serious adverse events were defined as Grade 3 or higher.
Arm/Group Title	Lenalidomide (Revlimid)
Arm/Group Description	Treatment will be initated at 25 mg/day taken in the morning. Dose adjustments may be made to alleviate toxicities.
All Cause Mortality
	Lenalidomide (Revlimid)
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Serious Adverse Events
	Lenalidomide (Revlimid)
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Neutropenia	10/25 (40%)
Leukopenia	6/25 (24%)
Thrombocytopenia	4/25 (16%)
Anemia	1/25 (4%)
Idiopathic Thrombocytopenic Purpura	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/25 (4%)
Social circumstances
Rash	1/25 (4%)
Vascular disorders
Pulmonary Embolism	2/25 (8%)
Other (Not Including Serious) Adverse Events
	Lenalidomide (Revlimid)
	Affected / at Risk (%)	# Events
Total	3/25 (12%)
General disorders
Fatigue	1/25 (4%)
Weight Loss	1/25 (4%)
Skin and subcutaneous tissue disorders
Rash	1/25 (4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.