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

University of Michigan Rogel Cancer Center

Status and phase

Enrolling

Phase 2

Conditions

Metastatic Thyroid Cancer

Treatments

Drug: Cyclophosphamide

Drug: Sirolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT03099356

HUM00126559 (Other Identifier)

UMCC 2017.013

Details and patient eligibility

About

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.

Enrollment

19 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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