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

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ClinicalTrials.gov Identifier: NCT03099356
Recruitment Status : Recruiting
First Posted : April 4, 2017
Last Update Posted : May 25, 2017
Sponsor:
Information provided by (Responsible Party):
University of Michigan Cancer Center

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 disease Intervention/treatment Phase
Metastatic Thyroid Cancer Drug: Cyclophosphamide Drug: Sirolimus Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
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 : April 27, 2017
Estimated Primary Completion Date : May 12, 2022
Estimated Study Completion Date : May 12, 2023

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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



Primary Outcome Measures :
  1. Percentage of patients that respond to treatment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03099356


Contacts
Contact: Francis Worden, M.D. 734-936-0453 fworden@umich.edu

Locations
United States, Michigan
University of Michigan Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Francis P Worden, MD    734-936-0453    fworden@umich.edu   
Contact: Cancer AnswerLine    1-800-865-1125    canceranswerline@umich.edu   
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Francis Worden, M.D. University of Michigan Cancer Center

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT03099356     History of Changes
Other Study ID Numbers: UMCC 2017.013
HUM00126559 ( Other Identifier: University of Michigan )
First Posted: April 4, 2017    Key Record Dates
Last Update Posted: May 25, 2017
Last Verified: May 2017

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:
Thyroid Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Sirolimus
Everolimus
Thyroid Diseases
Endocrine System Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents