Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer

Metastatic Thyroid Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03099356
• Other study ID #: UMCC 2017.013
• Secondary ID: HUM00126559
• Status: Recruiting
• Phase: Phase 2
• Start date: April 27, 2017
• Est. completion date: May 2025

Study information

• Verified date: January 2024
• Source: University of Michigan Rogel Cancer Center
• Contact: Cancer AnswerLine
• Phone: 1-800-865-1125
• Email: canceranswerline[@]umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 19
• Est. completion date: May 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• Willingness and ability to comply with scheduled visits, treatment plans, including willingness to take study medication, laboratory tests, and other study procedures

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

• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol

• Patients (male and female) having procreative potential who are not willing or not able to use adequate contraception or practicing abstinence

• Women who are pregnant or breast-feeding

• Patients residing in prison

Related Conditions & MeSH terms

• Metastatic Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

Drug:
• Cyclophosphamide
Cyclophosphamide 100 mg, PO, days 1-5 and 15-19
• Sirolimus
Sirolimus 4 mg, PO, days 1-28

Locations

Country	Name	City	State
United States	University of Michigan Cancer Center	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients that respond to treatment	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.	Patients will be followed for response until progression or up to 2 Years
Secondary	The number of patients that experience toxicity	The number of patients that experience toxicity by type will be reported.	Patients are followed for toxicity up to 30 days after the last dose of study drug
Secondary	Median overall survival time	The median duration of time from start of treatment until death	Patients will be followed until death or up to 2 years
Secondary	Median progression free survival time	The median duration of time from start of treatment until progression. Progression is defined as at least a 20% increase in the sum of the LD (longest diameter) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	Patients will be followed for response until progression or up to 2 Years