An Open Label Phase II Trial Evaluating the Efficacy of Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer

University of Michigan Rogel Cancer Center1 site in 1 country22 target enrollmentApril 27, 2017

ConditionsMetastatic Thyroid Cancer

InterventionsCyclophosphamide Sirolimus

DrugsCyclophosphamide Sirolimus

Overview

Phase: Phase 2
Intervention: Cyclophosphamide
Conditions: Metastatic Thyroid Cancer
Sponsor: University of Michigan Rogel Cancer Center
Enrollment: 22
Locations: 1
Primary Endpoint: Percentage of patients that respond to treatment
Status: Recruiting
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will be a non-randomized pilot trial using Cyclophosphamide and Sirolimus for the treatment of metastatic differentiated thyroid cancer. Patients will be treated with Sirolimus 4 mg, PO, days 1-28 as well as Cyclophosphamide 100 mg, PO, days 1-5 and 15-19. Cycle length will be 28 days. Patients will be monitored closely for toxicity and undergo imaging to evaluate efficacy once every 2 cycles.

Registry

clinicaltrials.gov

Start Date

April 27, 2017

End Date

December 1, 2026

Last Updated

9 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Michigan Rogel Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically documented differentiated thyroid cancer with or without metastases, not amenable to curative treatment; or the patient has documented refusal of curative treatment
•Measurable disease (\>10 mm) and have progression of disease based on RECIST criteria. Previously irradiated tumor lesions are not considered measurable unless they have progressed since radiation.
•Previous failure of Iodine-131 (131I) therapy or not candidates to receive 131I as assessed by treating physician.
•Age ≥ 18 years
•ECOG (Eastern Cooperative Oncology Group) performance status 0-2
•Life expectance of ≥ 12 weeks
•131I therapy not allowed within 24 weeks before entry (4 weeks if negative post-treatment scan)
•Adequate organ and marrow function
•Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment
•Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment

Exclusion Criteria

•Inability to obtain Foundation One testing on archival tissue, or, lack of previous Next Generation Sequencing
•Chemotherapy, tyrosine kinase inhibitor, or radiation therapy within 4 weeks
•Prior experimental therapy within 4 weeks of planned start of this trial
•131I therapy within 24 weeks before entry (4 weeks if negative post-treatment scan)
•Previous treatment with an mTOR inhibitor
•Patients who are currently receiving treatment with strong inhibitors or inducers of CYP3A4 or P-glycoprotein that cannot be discontinued at least one week prior to the start of treatment with Cyclophosphamide and Sirolimus
•Impairment of GI (gastrointestinal) function or GI disease that may significantly alter the absorption of study medications (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) including dependence on a G-Tube for administration of medications.
•A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment
•Patients with known sensitivities to either cyclophosphamide and/or sirolimus
•Patients with known urinary outflow obstruction

Arms & Interventions

Cyclophosphamide and Sirolimus

Sirolimus 4 mg, PO, days 1-28 as well as Cyclophosphamide 100 mg, PO, days 1-5 and 15-19

Intervention: Cyclophosphamide

Cyclophosphamide and Sirolimus

Sirolimus 4 mg, PO, days 1-28 as well as Cyclophosphamide 100 mg, PO, days 1-5 and 15-19

Intervention: Sirolimus

Outcomes

Primary Outcomes

Percentage of patients that respond to treatment

Time Frame: Patients will be followed for response until progression or up to 2 Years

The primary measure of efficacy will be the overall response rate (ORR) which is defined as those achieving either complete response (CR) or partial response (PR). Partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Complete response is defined as Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart (there can be no appearance of new lesions) and the disappearance of all non-target lesions and normalization of tumor marker level.

Secondary Outcomes

The number of patients that experience toxicity(Patients are followed for toxicity up to 30 days after the last dose of study drug)
Median overall survival time(Patients will be followed until death or up to 2 years)
Median progression free survival time(Patients will be followed for response until progression or up to 2 Years)