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Protocol Details

Phase II Trial of Pembrolizumab in Recurrent or Metastatic Medullary Thyroid Cancer

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

17-C-0061

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women;
Fetuses;
Children

Keywords

Anti-PD1/PDL1;
Vaccine Therapy;
TKI-Naive

Recruitment Keyword(s)

None

Condition(s)

Medullary Thyroid Cancer (MTC)

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Pembrolizumab

Supporting Site

National Cancer Institute

Background:

Medullary thyroid cancer (MTC) is a tumor of the thyroid gland. Surgery is the only current treatment to cure it. The drug pembrolizumab (MK-3475) is a new type of cancer therapy. It works by allowing the immune system to detect and kill tumor cells.

Objective:

To test how pembrolizumab affects people with MTC and if it can offer them clinical benefit.

Eligibility:

People ages 18 and older with MTC

Patients who have recurrent or metastatic MTC, for whom surgery is not a curative option

Patients with some imaging evidence of MTC

Patients with minimal symptoms related to MTC

Design:

Participants will be screened with:

-Medical history

-Physical exam

-Blood, urine, and heart tests

-CT scan or MRI: They lie in a machine that takes pictures of the body.

-Bone scan

Participants will be put in a group based on their treatment history:

-Group 1 if they have had an immune stimulating cancer vaccine

-Group 2 if they have had no vaccine

Participants will receive the study drug as a 30-minute IV infusion every 3 weeks. Treatment will continue for up to 2 years as long as they tolerate it and their disease does not get worse.

Participants will have physical exams and blood tests on the day of each infusion. They will have CT and bone scans every 3 months.

Participants may save biopsies before treatment and after starting treatment.

Participants will have a final visit 3-4 weeks after stopping treatment. This will include a physical exam and blood and heart tests.

After this study, participants will can join a long-term follow-up study.

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Eligibility

INCLUSION CRITERIA:

-Diagnosis: Patients must have histologically confirmed medullary thyroid cancer by the Laboratory of Pathology or a pathology report and history consistent with medullary thyroid cancer. It is not uncommon for a secondary, minor pathologic focus of another form of thyroid cancer to be coincidentally found in 15-20% of patients with medullary thyroid cancer. In such cases, eligibility is based on the discretion of the investigator.

-Patients must have evidence of metastatic medullary thyroid cancer including disease that is evaluable on bone, CT scan or MRI. (Patients who are surgical candidates and potentially rendered disease free with surgical resection are not eligible.)

-Patients must have elevated calcitonin levels greater than 40 pg/mL

-Patients must have minimal or no disease related-symptoms (Minimal symptoms will include those that do not affect activities of daily living or pain that does not require regularly scheduled narcotics.)

-Patients must have evaluable disease on imaging

-No history of seizures, encephalitis, or multiple sclerosis.

-Age greater than or equal to 18 years

-ECOG performance status of 0-1 at study entry (Karnofsky greater than or equal to 70).

-Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

-Female subjects of childbearing potential must be willing to use an adequate method of contraception, Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

-Male subjects of childbearing potential must agree to use an adequate method of contraception. Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

-Willing to travel to the NIH for follow-up visits

-Able to understand and sign informed consent.

-Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation.

-Adequate Organ Function Laboratory Values

--Hematological

---Absolute neutrophil count (ANC) greater than or equal to1,000 /mcL

--Platelets greater than or equal to 100,000 / mcL

--Hemoglobin greater than or equal to 9 g/dL or greater than or equal to 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)

--Renal

---Serum creatinine less than or equal to1.5 X upper limit of normal (ULN) OR

---Measured or calculated* creatinine clearance (GFR can also be used in place of creatinine or CrCl) greater than or equal to 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN

--Hepatic

---Serum total bilirubin less than or equal to 1.5 X ULN OR Direct bilirubin less than or equal to ULN for subjects with total bilirubin levels > 1.5 ULN

---AST (SGOT) and ALT (SGPT) less than or equal to 2.5 X ULN OR less than or equal to 5 X ULN for subjects with liver metastases

---Albumin >2.5 mg/dL

--Coagulation

---International Normalized Ratio (INR) or Prothrombin Time (PT) less than or equal to1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

---Activated Partial Thromboplastin Time (aPTT) less than or equal to1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

*Creatinine clearance should be calculated per Cockcroft-Gault equation

EXCLUSION CRITERIA:

-Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.

-Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

-Has a known history of active TB (Bacillus Tuberculosis)

-Hypersensitivity to pembrolizumab or any of its excipients.

-Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

-Has had prior targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with less than or equal to Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

-Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

-Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable for 6 months (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

-Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.

-Has an active infection requiring systemic therapy.

-Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

-Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

-Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

-Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

-Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

-Has active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

-Has received a live vaccine within 30 days of planned start of study therapy

-Concurrent use of systemic steroids, except for physiologic doses of systemic steroid replacement or local (topical, nasal, eye drops or inhaled) steroid use. Limited doses of systemic steroids (e.g., in patients with exacerbations of reactive airway disease or to prevent IV contrast allergic reaction or anaphylaxis in patients who have known contrast allergies) are allowed.

-Serious inter-current medical illness which would interfere with the ability of the patient to carry out the treatment program.

-Patients with second malignancy within 3 years of enrollment; Patients curatively treated non-melanoma skin cancers or carcinoma in situ of the bladder, are not excluded. Patients with MEN2 and a history of pheochromocytoma will also not be excluded. In addition patients with prostate cancer who do not require systemic therapy will not be excluded. (A secondary, minor pathologic focus of another form of thyroid cancer may be coincidentally found in 15-20% of patients with medullary thyroid cancer. In such cases, eligibility is based on the discretion of the investigator.)

-Patients with previous history of vandetanib or cabozantinib treatment for more than 28 days of treatment (patients have discontinued treatment for 28 days before enrolling).


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Ravi A. Madan, M.D.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 13N240B
10 Center Drive
Bethesda, Maryland 20892
(301) 480-7168
rm480i@nih.gov

Helen T. Owens, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 13N244
10 Center Drive
Bethesda, Maryland 20892
(240) 760-7965
howens@mail.cc.nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT03072160

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