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

Sponsor
University of Michigan Rogel Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT03099356
Collaborator
(none)
19
Enrollment
1
Location
1
Arm
72.5
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
19 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Apr 27, 2017
Anticipated Primary Completion Date :
May 12, 2022
Anticipated Study Completion Date :
May 12, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Cyclophosphamide and Sirolimus

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

Drug: Cyclophosphamide
Cyclophosphamide 100 mg, PO, days 1-5 and 15-19

Drug: Sirolimus
Sirolimus 4 mg, PO, days 1-28

Outcome Measures

Primary Outcome Measures

  1. Percentage of patients that respond to treatment [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 Outcome Measures

  1. The number of patients that experience toxicity [Patients are followed for toxicity up to 30 days after the last dose of study drug]

    The number of patients that experience toxicity by type will be reported.

  2. Median overall survival time [Patients will be followed until death or up to 2 years]

    The median duration of time from start of treatment until death

  3. Median progression free survival time [Patients will be followed for response until progression or up to 2 Years]

    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.

Eligibility Criteria

Criteria

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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of Michigan Cancer CenterAnn ArborMichiganUnited States48109

Sponsors and Collaborators

  • University of Michigan Rogel Cancer Center

Investigators

  • Principal Investigator: Paul Swiecicki, M.D., University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier:
NCT03099356
Other Study ID Numbers:
  • UMCC 2017.013
  • HUM00126559
First Posted:
Apr 4, 2017
Last Update Posted:
Dec 16, 2021
Last Verified:
Dec 1, 2021
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 16, 2021