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Metastatic Medullary Thyroid CancerPhase 1NCT04877613

GFRα4 CAR T Cells in MTC Patients

A Phase 1 study testing single dose of CART-GFRa4 cells, Fludarabine and Cyclophosphamide in people with Metastatic Medullary Thyroid Cancer and Recurrent Thyroid Gland Medullary Carcinoma, run by University of Pennsylvania at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is an open-label phase 1 study to assess the safety and feasibility of autologous T cells expressing a single-chain scFv targeting GFRα4 with tandem TCR/CD3ζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-GFRa4 cells") in patients with incurable medullary thyroid cancer (MTC). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
single dose of CART-GFRa4 cells, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
19 Aug 2021to 1 Jun 2039
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed, written informed consent
  • Male or female age ≥ 18 years
  • Histologically or cytologically confirmed diagnosis of medullary thyroid cancer (MTC).
  • Incurable recurrent/metastatic disease that is progressive after at least 1 prior tyrosine kinase inhibitor (TKI) containing regimen, or the patient was intolerant of or declined such therapy.
  • Adequate organ function defined as:
  • Serum creatinine ≤ 2.5 mg/dl or estimated creatinine clearance ≥ 30 ml/min and not on dialysis.
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  • AST ≤ 5x upper limit of normal range and total bilirubin ≤ 2.0 mg/dl; except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome.
  • Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
  • Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen greater than 92% on room air.
  • ECOG Performance Status that is either 0 or 1.
  • Toxicities from prior therapies must have recovered to grade ≤ 2 according to the CTCAE 5.0 criteria or to the patient's prior baseline.
  • Patients must have evaluable disease as defined by RECIST 1.1.
  • Subjects of reproductive potential must agree to use acceptable birth control methods.

Who cannot join

  • Evidence of active hepatitis B or hepatitis C infection. The following would not qualify as an active infection, thus would not exclude the subject from participating
  • Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis for potential HBV reactivation.
  • Positive HCV serology with quantitative PCR for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment.
  • Any other active, uncontrolled infection.
  • Any prior history of moderate to severe (Grade 2 or higher) pneumonitis.
  • Subjects with chronic kidney disease with Grade 2 or higher renal impairment (eGFR or CrCl 59-30 ml/min/1.73 m2).
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  • Class III/IV cardiovascular disability according to the New York Heart Association Classification.
  • Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
  • Planned concurrent treatment with systemic high dose corticosteroids. Patients may be on a stable low dose of steroids (≤10mg equivalent of prednisone). Use of inhaled steroids is allowable. Corticosteroid treatment as anti-emetic prophylaxis on the day of lymphodepleting chemotherapy administration is allowed per institutional practice.
  • Any moderate to severe skin rash or allergies requiring systemic treatment.
  • Receipt of immune checkpoint inhibitors within 2 months prior to physician-investigator confirmation of eligibility - Retired with Protocol Version 3.
  • Pregnant or nursing (lactating) women.
  • Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurological diseases (such as MS or Parkinson's) will be excluded.
  • Have any history of prior or active central nervous system (CNS) involvement (e.g., leptomeningeal disease, parenchymal masses) with MTC. Screening for this (e.g., with lumbar puncture and/or brain MRI) is not required unless suspicious symptoms and/or radiographic findings are present. Subjects with calvarial metastatic disease that extends intracranially and involves the dura will be excluded, even if CSF is negative for MTC.
  • Known seizure disorder or history of prior seizures requiring medication.
  • History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Phase I Trial of GFRα4 CAR T Cells in Adult Patients With Recurrent or Metastatic Medullary Thyroid Cancer

This is an open-label phase 1 study to assess the safety and feasibility of autologous T cells expressing a single-chain scFv targeting GFRα4 with tandem TCR/CD3ζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-GFRa4 cells") in patients with incurable medullary thyroid cancer (MTC).

Being tested
single dose of CART-GFRa4 cells, Fludarabine, Cyclophosphamide
Medical subject headings
Carcinoma, Medullary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • single dose of CART-GFRa4 cellsDrug

    Intravenous infusion of lentiviral transduced autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity towards GFRa4 with fludarabine and cyclophosphamide.

  • FludarabineDrug

    Lymphodepletion

  • CyclophosphamideDrug

    Lymphodepletion

Study groups in NCT04877613
Study groupRoleWhat they receive
Cohort 1: single dose of 5x10^7 CART-GFRa4 cells via intravenous infusionExperimentalNot described
Receives: Drug: single dose of CART-GFRa4 cells; Drug: Fludarabine; Drug: Cyclophosphamide
Cohort -1: single dose of 2x10^7 CART-GFRa4 cells via intravenous infusionExperimentalNot described
Receives: Drug: single dose of CART-GFRa4 cells; Drug: Fludarabine; Drug: Cyclophosphamide
Cohort 2: single dose of 1x10^8 CART-GFRa4 cells via intravenous infusionExperimentalNot described
Receives: Drug: single dose of CART-GFRa4 cells; Drug: Fludarabine; Drug: Cyclophosphamide
Cohort 3: single fixed dose of 3x10^8 CART-GFRa4 cells via intravenous infusionExperimentalNot described
Receives: Drug: single dose of CART-GFRa4 cells; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0.

    Measured: 15 years

Secondary outcomes (6)

  1. Percentage of manufacturing products that meet release criteria.

    Measured: 3 months

  2. Number of subjects who have a response (ORR)

    Measured: 12 months

  3. Best Overall Response (BOR)

    Measured: 12 months

  4. Duration of Response (DOR)

    Measured: 12 months

  5. Overall survival (OS)

    Measured: 12 months

  6. Progression-free survival (PFS)

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2021
  2. Study start19 Aug 2021
  3. Primary completion1 Jun 2039 (estimated)
  4. Study completion1 Jun 2039 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Health services research
Allocation
Non-randomised
Intervention model
Sequential
Model description
The is a Phase I dose finding study to determine the safety of CART-GFRa4 cells. Dose escalation and determination of maximum tolerated dose (MTD) will be based on the standard 3+3 design to explore 3 possible dose levels.
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04877613
Sponsor's protocol ID
IRB# 848848; UPCC# 12320
Status last verified
Jul 2026
First submitted
3 May 2021
Last updated
22 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing single dose of CART-GFRa4 cells, Fludarabine and Cyclophosphamide in people with Metastatic Medullary Thyroid Cancer and Recurrent Thyroid Gland Medullary Carcinoma, run by University of Pennsylvania at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0. (time frame: 15 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04877613.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.

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