Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer
Primary Purpose
Metastatic Thyroid Cancer
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Sirolimus
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Thyroid Cancer
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
- 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
Sites / Locations
- University of Michigan Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cyclophosphamide and Sirolimus
Arm Description
Sirolimus 4 mg, PO, days 1-28 as well as Cyclophosphamide 100 mg, PO, days 1-5 and 15-19
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
The number of patients that experience toxicity
The number of patients that experience toxicity by type will be reported.
Median overall survival time
The median duration of time from start of treatment until death
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.
Full Information
NCT ID
NCT03099356
First Posted
March 28, 2017
Last Updated
August 30, 2023
Sponsor
University of Michigan Rogel Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT03099356
Brief Title
Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 27, 2017 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Thyroid Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cyclophosphamide and Sirolimus
Arm Type
Experimental
Arm Description
Sirolimus 4 mg, PO, days 1-28 as well as Cyclophosphamide 100 mg, PO, days 1-5 and 15-19
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide 100 mg, PO, days 1-5 and 15-19
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Intervention Description
Sirolimus 4 mg, PO, days 1-28
Primary Outcome Measure Information:
Title
Percentage of patients that respond to treatment
Description
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.
Time Frame
Patients will be followed for response until progression or up to 2 Years
Secondary Outcome Measure Information:
Title
The number of patients that experience toxicity
Description
The number of patients that experience toxicity by type will be reported.
Time Frame
Patients are followed for toxicity up to 30 days after the last dose of study drug
Title
Median overall survival time
Description
The median duration of time from start of treatment until death
Time Frame
Patients will be followed until death or up to 2 years
Title
Median progression free survival time
Description
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.
Time Frame
Patients will be followed for response until progression or up to 2 Years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cancer AnswerLine
Phone
1-800-865-1125
Email
canceranswerline@umich.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Paul Swiecicki, M.D.
Email
pswiecic@med.umich.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Swiecicki, M.D.
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul Swiecicki, M.D.
Email
pswiecic@med.umich.edu
First Name & Middle Initial & Last Name & Degree
Francis Worden, M.D.
Phone
734-936-0453
Email
fworden@umich.edu
First Name & Middle Initial & Last Name & Degree
Paul Swieciki, M.D.
12. IPD Sharing Statement
Learn more about this trial
Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer
We'll reach out to this number within 24 hrs