Clinical Trials /

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

NCT03099356

Description:

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.

Related Conditions:
  • Well-Differentiated Thyroid Gland Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.013
  • SECONDARY ID: HUM00126559
  • NCT ID: NCT03099356

Conditions

  • Metastatic Thyroid Cancer

Interventions

DrugSynonymsArms
CyclophosphamideCyclophosphamide and Sirolimus
SirolimusCyclophosphamide and Sirolimus

Purpose

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.

Trial Arms

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

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients that respond to treatment
Time Frame:Patients will be followed for response until progression or up to 2 Years
Safety Issue:
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.

Secondary Outcome Measures

Measure:The number of patients that experience toxicity
Time Frame:Patients are followed for toxicity up to 30 days after the last dose of study drug
Safety Issue:
Description:The number of patients that experience toxicity by type will be reported.
Measure:Median overall survival time
Time Frame:Patients will be followed until death or up to 2 years
Safety Issue:
Description:The median duration of time from start of treatment until death
Measure:Median progression free survival time
Time Frame:Patients will be followed for response until progression or up to 2 Years
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

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