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

NCT03099356 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: UMCC 2017.013HUM00126559
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• The number of patients that experience toxicity

  Patients are followed for toxicity up to 30 days after the last dose of study drug

• Median overall survival time

  Patients will be followed until death or up to 2 years

• Median progression free survival time

  Patients will be followed for response until progression or up to 2 Years

Study Arms (1)

Cyclophosphamide and Sirolimus

EXPERIMENTAL

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

Drug: Cyclophosphamide; Drug: Sirolimus

Interventions

Cyclophosphamide DRUG

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

Cyclophosphamide and Sirolimus

Sirolimus DRUG

Sirolimus 4 mg, PO, days 1-28

Cyclophosphamide and Sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• I 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

You may not qualify if:

• 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
• I 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

Cyclophosphamide; Sirolimus

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones

Study Officials

• Paul Swiecicki, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer AnswerLine

CONTACT

1-800-865-1125; canceranswerline@umich.edu

Paul Swiecicki, M.D.

CONTACT

pswiecic@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 4, 2017
• Study Start: April 27, 2017
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 1, 2025

Record last verified: 2025-07

Locations

US (1)