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

An Open Label Phase II Trial Evaluating the Efficacy of Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Thyroid Cancer
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Sirolimus

• Study Type: Interventional
• Enrollment (Estimated): 19
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cancer AnswerLine; Phone Number: 1-800-865-1125; Email: canceranswerline@umich.edu
• Study Contact Backup: Name: Paul Swiecicki, M.D.; Email: pswiecic@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Cancer Center
      • Contact: Paul Swiecicki, M.D.; Email: pswiecic@med.umich.edu
      • Contact: Francis Worden, M.D.; Phone Number: 734-936-0453; Email: fworden@umich.edu
      • Principal Investigator: Paul Swieciki, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2017
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: March 28, 2017
• First Submitted That Met QC Criteria: March 28, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Cyclophosphamide; Sirolimus
• Other Study ID Numbers: UMCC 2017.013; HUM00126559 (Other Identifier: University of Michigan)

Drug and device information, study documents

• 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