Malignant MelanomaEarly Phase 1NCT03060356
Autologous T Cells Expressing MET scFv CAR (RNA CART-cMET)
A Early Phase 1 study testing T cells modified with RNA anti -cMET CAR in people with Malignant Melanoma and Breast Cancer, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred to as "RNA CART-cMET") in patients with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma, Breast Cancer
- What is being tested?
- T cells modified with RNA anti -cMET CAR
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Dec 2016to 27 Mar 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- Unresectable histologically confirmed stage III/IV melanoma or metastatic or locally advanced unresectable ER and PR negative, HER2 neu nonamplified by IHC and/or FISH breast carcinoma
- cMET expression in ≥ 30% tumor cells as demonstrated on immunohistochemistry analysis at the University of Pennsylvania. MET IHC may be performed on tissue from screening biopsy, or archival slides of a metastatic deposit or primary tumor. Punch biopsy or percutaneous core biopsy will be offered to obtain tissue as required for this purpose.
- Patients must have measureable disease as defined by RECIST 1.1 criteria; must have CT scan of chest, abdomen, pelvis within 1 month of enrollment that demonstrates measurable disease by RECIST 1.1 criteria in a tumor other than the one being potentially biopsied and resected for correlative studies
- Failure of at least one prior standard of care therapy for advanced stage disease
- If previously treated with any form of immunotherapy (including agents targeting PD1 or CTLA4, oncolytic viruses) the last administered treatment must be at least 2 weeks prior to enrollment
- Males or female patients age > 18 years old
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- Eastern Cooperative Oncology Group (ECOG) Clinical Performance Status 0 or 1
- Adequate hematologic and organ function as defined by:
- WBC > 3.0 and ANC >1500
- Plt > 75,000 (no transfusion permitted within 2 weeks to achieve this goal)
- Hgb > 9 g/dl (transfusions are permitted to achieve this goal)
- serum creatinine ≤ 1.5 times upper limit of normal
- Total bilirubin ≤ 2times upper limit of normal
- ALT and AST ≤ 2 times upper limit of normal
- Cardiac ejection fraction of >40% as measured by resting echocardiogram
- Women of child bearing potential must have a negative serum or urine pregnancy test and agree to use appropriate contraception from enrollment through the duration of the trial. Men must agree to use appropriate contraception from enrollment through the duration of the trial.
- Patients must provide written informed consent.
Who cannot join
- Known metastatic tumor encasing a great vessel or at risk for imminently causing spinal cord compression
- Known HIV-1/HIV-2 infection
- Known active infection with Hepatitis B virus or Hepatitis C virus
- Received an experimental therapy within 30 days of enrollment
- Pregnant women or lactating women
- History of alcohol abuse or illicit drug use within 12 months of enrollment
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- Clinically significant comorbid disease or other underlying condition, including significant active infection, in the opinion of the PI or sub-investigators, would contraindicate study therapy or interfere with interpretation of study results
- Significant psychiatric disorder and/or any other reason in the Investigator's opinion that would jeopardize protocol compliance or compromise the patient's ability to give informed consent.
- Patients with known allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
- Patients with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management within 2 weeks of the Screening/Enrollment visit.
- Having received prior genetically manipulated T-cells in prior clinical trial
- History of autoimmune disease (including but not limited to: systemic lupus erythematosis, Sjogren syndrome, rheumatoid arthritis, psoriasis multiple sclerosis, inflammatory bowel disease etc).
- History of immune related adverse event with previous immunotherapy.
- Chronic use of therapeutic anti-coagulants such as coumadin, heparin, or lovenox
- Symptomatic or untreated CNS metastases. Pts with previously treated CNS metastases are eligible if lesions are radiographically/clinically stable without requirement of steroids within 4 weeks prior to treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Clinical Trial of Autologous cMET Redirected T Cells Administered Intravenously in Patients With Melanoma & Breast Carcinoma
This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred to as "RNA CART-cMET") in patients with advanced melanoma or breast carcinoma.
Read the detailed description
This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred to as "RNA CART-cMET") in patients with advanced melanoma or breast carcinoma. Subjects will be treated with IV administration of the RNA transduced anti-cMET CAR T cells for a total of up to six doses over a 2 week period.
Each dose is 1x108 total T cells modified with RNA anti-cMET CAR. All subjects in both the melanoma and breast carcinoma arms will receive up to 6 doses of RNA CART-cMET cells, with no lymphodepleting chemotherapy administered prior to cell infusion Cell numbers are based on total cells with a portion of them having CAR expression depending on transduction efficiency and determined by flow cytometry Based on the product release criteria, at least 20% of the total cells will express the anti-cMET CAR. Treatment limiting toxicity (TLT). Adverse event reporting will begin at the start of the first dose of RNA CART-cMET and will continue until 4 months after the first infusion, or until another alternative therapy is initiated, whichever occurs earlier. Subjects will be continually reassessed for evidence of acute and cumulative toxicity.
- Conditions
- Malignant Melanoma, Breast Cancer
- Being tested
- T cells modified with RNA anti -cMET CAR
- Medical subject headings
- Melanoma, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T cells modified with RNA anti -cMET CARBiological
Intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains
| Study group | Role | What they receive |
|---|---|---|
| Melanoma | Active comparator | Intravenous infusion 1x10^8 total T cells modified with RNA anti-cMET CAR Receives: Biological: T cells modified with RNA anti -cMET CAR |
| Breast | Active comparator | Intravenous infusion 1x10^8 total T cells modified with RNA anti-cMET CAR Receives: Biological: T cells modified with RNA anti -cMET CAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 in melanoma and breast cancer subjects
Measured: from day 0 - month 4
Secondary outcomes (4)
Objective overall response rate by clinical exam for visible cutaneous tumors
Measured: day 25 and month 4
Objective overall response rate by radiologic imaging using RECIST 1.1
Measured: day 25 and month 4
Estimate the activity of RNA CART-cMET in subjects who receive at least 1 dose of cells by objective response rate using RECIST 1.1 criteria
Measured: day -7 and day 11
Estimate the activity of RNA CART-cMET in subjects who receive at least 1 dose of cells by objective response rate using pathological evaluation of resected or biopsied tissue
Measured: day -7 and day 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study start21 Dec 2016
- Primary completion27 Mar 2020
- Study completion27 Mar 2020
Why it stopped: Halt in funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tara C. Mitchell, MD, Principal investigator, University of Pennaylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03060356
- Sponsor's protocol ID
- UPCC 11916, 825376
- Status last verified
- Jun 2023
- First submitted
- 7 Feb 2017
- Last updated
- 22 Jun 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Shah PD, Huang AC, Xu X, Orlowski R, Amaravadi RK, Schuchter LM, Zhang P, Tchou J, Matlawski T, Cervini A, Shea J, Gilmore J, Lledo L, Dengel K, Marshall A, Wherry EJ, Linette GP, Brennan A, Gonzalez V, Kulikovskaya I, Lacey SF, Plesa G, June CH, Vonderheide RH, Mitchell TC. Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma. Cancer Res Commun. 2023 May 9;3(5):821-829. doi: 10.1158/2767-9764.CRC-22-0486. eCollection 2023 May.
PubMed 37377890
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial of Autologous cMET Redirected T Cells Administered Intravenously in Patients With Melanoma & Breast Carcinoma
- ClinicalTrials.gov ID
- NCT03060356
- Acronym / sponsor ID
- UPCC 11916, 825376
- Conditions
- Malignant Melanoma, Breast Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Halt in funding
- Enrolment
- 77 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 21 Dec 2016 (actual)
- Primary completion
- 27 Mar 2020 (actual)
- Study completion
- 27 Mar 2020 (actual)
- First posted
- 23 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred to as "RNA CART-cMET") in patients with advanced melanoma or breast carcinoma.
Detailed description
This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred to as "RNA CART-cMET") in patients with advanced melanoma or breast carcinoma. Subjects will be treated with IV administration of the RNA transduced anti-cMET CAR T cells for a total of up to six doses over a 2 week period.
Each dose is 1x108 total T cells modified with RNA anti-cMET CAR. All subjects in both the melanoma and breast carcinoma arms will receive up to 6 doses of RNA CART-cMET cells, with no lymphodepleting chemotherapy administered prior to cell infusion Cell numbers are based on total cells with a portion of them having CAR expression depending on transduction efficiency and determined by flow cytometry Based on the product release criteria, at least 20% of the total cells will express the anti-cMET CAR. Treatment limiting toxicity (TLT). Adverse event reporting will begin at the start of the first dose of RNA CART-cMET and will continue until 4 months after the first infusion, or until another alternative therapy is initiated, whichever occurs earlier. Subjects will be continually reassessed for evidence of acute and cumulative toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melanoma | Active comparator | Biological: T cells modified with RNA anti -cMET CARIntravenous infusion 1x10^8 total T cells modified with RNA anti-cMET CAR |
| Breast | Active comparator | Biological: T cells modified with RNA anti -cMET CARIntravenous infusion 1x10^8 total T cells modified with RNA anti-cMET CAR |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Unresectable histologically confirmed stage III/IV melanoma or metastatic or locally advanced unresectable ER and PR negative, HER2 neu nonamplified by IHC and/or FISH breast carcinoma
- cMET expression in ≥ 30% tumor cells as demonstrated on immunohistochemistry analysis at the University of Pennsylvania. MET IHC may be performed on tissue from screening biopsy, or archival slides of a metastatic deposit or primary tumor. Punch biopsy or percutaneous core biopsy will be offered to obtain tissue as required for this purpose.
- Patients must have measureable disease as defined by RECIST 1.1 criteria; must have CT scan of chest, abdomen, pelvis within 1 month of enrollment that demonstrates measurable disease by RECIST 1.1 criteria in a tumor other than the one being potentially biopsied and resected for correlative studies
- Failure of at least one prior standard of care therapy for advanced stage disease
- If previously treated with any form of immunotherapy (including agents targeting PD1 or CTLA4, oncolytic viruses) the last administered treatment must be at least 2 weeks prior to enrollment
Key exclusion criteria (15 listed)
- Known metastatic tumor encasing a great vessel or at risk for imminently causing spinal cord compression
- Known HIV-1/HIV-2 infection
- Known active infection with Hepatitis B virus or Hepatitis C virus
- Received an experimental therapy within 30 days of enrollment
- Pregnant women or lactating women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| T cells modified with RNA anti -cMET CARIntravenously administered, RNA electroporated autologous T cells expressing MET chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains | Biological | Breast, Melanoma |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 in melanoma and breast cancer subjects
Time frame: from day 0 - month 4
4 secondary outcomes
Objective overall response rate by clinical exam for visible cutaneous tumors
Time frame: day 25 and month 4
Objective overall response rate by radiologic imaging using RECIST 1.1
Time frame: day 25 and month 4
Estimate the activity of RNA CART-cMET in subjects who receive at least 1 dose of cells by objective response rate using RECIST 1.1 criteria
Time frame: day -7 and day 11
Estimate the activity of RNA CART-cMET in subjects who receive at least 1 dose of cells by objective response rate using pathological evaluation of resected or biopsied tissue
Time frame: day -7 and day 11
Results and safety
The study was stopped early (reason given: Halt in funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Derived from this study: PubMed 37377890Shah PD, Huang AC, Xu X, Orlowski R, Amaravadi RK, Schuchter LM, Zhang P, Tchou J, Matlawski T, Cervini A, Shea J, Gilmore J, Lledo L, Dengel K, Marshall A, Wherry EJ, Linette GP, Brennan A, Gonzalez V, Kulikovskaya I, Lacey SF, Plesa G, June CH, Vonderheide RH, Mitchell TC. Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma. Cancer Res Commun. 2023 May 9;3(5):821-829. doi: 10.1158/2767-9764.CRC-22-0486. eCollection 2023 May.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tara C. Mitchell, MD principal investigator
University of Pennaylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing T cells modified with RNA anti -cMET CAR in people with Malignant Melanoma and Breast Cancer, 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 17 inclusion and 15 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: stopped early, as of the sponsor's last update on 22 Jun 2023. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Halt in funding). Results are not available in the source record.
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?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 in melanoma and breast cancer subjects (time frame: from day 0 - month 4). 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 NCT03060356, which also lists 1 linked publication.
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 Jun 2023.