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Trial record 8 of 97 for:    avid

RAI Plus Immunotherapy for Recurrent/Metastatic Thyroid Cancers

This study is currently recruiting participants.
Verified September 2017 by Memorial Sloan Kettering Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT03215095
First Posted: July 12, 2017
Last Update Posted: October 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
AstraZeneca
MedImmune LLC
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
  Purpose
The purpose of this study is to find out what effects, good and/or bad, a drug called durvalumab combined with Thyrogen-stimulated RAI, has on the patient and thyroid cancer. Durvalumab is a drug that has been developed to activate the immune system by blocking a protein called programmed death ligand-1 (PD-L1) that can be present on tumor and normal cells, including immune cells.

Condition Intervention Phase
Thyroid Cancer Drug: Durvalumab (Medi4736) Radiation: Radioiodine (RAI) Early Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
This is a pilot study with the primary objective to assess the safety of administering the PD-L1 targeting agent durvalumab in combination with recombinant human thyroid stimulating hormone (rhTSH, Thyrogen) stimulated/prepared radioiodine (RAI; 131I) therapy in patients with RAI-avid (RAIA) recurrent and/or metastatic (R/M) thyroid cancer.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Radioiodine (RAI) in Combination With Durvalumab (Medi4736) for RAI-avid, Recurrent/Metastatic Thyroid Cancers

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • number of patients with Dose-Limiting Toxicity (DLTs) [ Time Frame: 6 weeks beginning from the first durvalumab ]
    Grading of DLTs will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.


Secondary Outcome Measures:
  • Best Overall Response [ Time Frame: 2 years ]
    Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)


Estimated Enrollment: 11
Actual Study Start Date: July 10, 2017
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radioiodine (RAI) in Combination with Durvalumab (Medi4736)
Enrolled patients will be treated with durvalumab 1500 mg IV every 4 weeks. In Cycle 1/Week 3, Thyrogen 0.9 mg IM will be administered on two consecutive calendar days followed by 100 mCi (+/- 10 mCi) of RAI the next calendar day. Durvalumab will be continued every 4 weeks.
Drug: Durvalumab (Medi4736)
durvalumab 1500 mg IV every 4 weeks
Radiation: Radioiodine (RAI)
100 mCi (+/- 10 mCi) of 131I will be administered a day after Thyrogen injections have been administered for two consecutive calendar days.

  Eligibility

Information from the National Library of Medicine

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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:

  • Patients must have histologically or cytologically confirmed thyroid carcinoma of follicular origin (including papillary, follicular, hurthle cell or poorly differentiated subtypes and their respective variants).
  • Diagnosis of recurrent and/or metastatic thyroid cancer
  • At least one RAI-avid lesion identified on a radioiodine scan (a diagnostic, post-therapy, or post-ablation scan) performed <24 months prior to study registration. (Both RAI-sensitive and RAI-refractory patients are eligible if at least one tumor with RAI avidity of any degree can be identified within these parameters.)
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease. Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment.
  • ECOG Performance Status (PS) 0 or 1. (or Karnofsky ≥60%)
  • Age ≥ 18 years at time of study entry
  • Adequate normal organ and marrow function as defined below:

    • Hemoglobin ≥ 9.0 g/dL
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
    • Platelet count ≥ 100 x 10^9/L (>100,000 per mm^3)
    • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.)
    • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
    • Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
  • Males:

Creatinine CL (mL/min) = Weight (kg) x (140 - Age) . 72 x serum creatinine (mg/dL)

  • Females:

Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)

  • Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Patients must agree to undergo two research biopsies of (a) malignant lesion(s). The investigator must also judge that the patient has tumor(s) safely accessible for biopsy. Patients may be exempt from the second biopsy if after the performance of the first biopsy it is felt that a second biopsy would be unsafe for the patient. If the patient has only one RECIST measureable target lesion for response assessment, research biopsies must not be performed on that target lesion.
  • Availability of archival tumor tissue from the thyroid cancer primary or metastasis (a tissue block or a minimum of 30 unstained slides would be required. Patients with less archival tissue available may still be eligible for the study after discussion with the MSK Principal Investigator.)

Exclusion Criteria:

  • 131I therapy < 6 months prior to initiation of therapy on this protocol. A diagnostic study using < 10 mCi of 131I is not considered 131I therapy.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
  • History of pneumonitis.
  • External beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol.
  • Chemotherapy, immunotherapy, targeted therapy, monoclonal antibodies, tumor embolization, or other investigational agent within 28 days prior to the first dose of study drug.
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  • Any unresolved toxicity CTCAE grade ≥ 2 from previous anti-cancer therapy. Exceptions include hearing loss, peripheral neuropathy, and alopecia.
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
  • Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with a history of autoimmune thyroid disease are not excluded. Subjects with vitiligo or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.
  • History of hypersensitivity to durvalumab or any excipient.
  • History of hypersensitivity to thyrotropin alpha (Thyrogen).
  • Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone).
  • Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration. Those that have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
  • Known history of active tuberculosis.
  • History of leptomeningeal carcinomatosis, brain metastases, or spinal cord compression.
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
  • Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Subjects with uncontrolled seizures.
  Contacts and Locations
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): NCT03215095


Contacts
Contact: Alan Ho, MD, PhD 646-888-4235 hoa@mskcc.org
Contact: David Pfister, MD 646-888-4232

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Alan Ho, MD. PhD    646-888-4235      
Contact: David Pfister, MD    646-888-4232      
Principal Investigator: Alan Ho, MD, PhD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
AstraZeneca
MedImmune LLC
Investigators
Principal Investigator: Alan Ho, MD, PhD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03215095     History of Changes
Other Study ID Numbers: 17-218
First Submitted: July 11, 2017
First Posted: July 12, 2017
Last Update Posted: October 2, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Radioiodine (RAI)
Durvalumab (Medi4736)
RAI-avid
17-218

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs