MelanomaPhase 1TORCHNCT04187872
LITT and Pembrolizumab in Recurrent Brain Metastasis
A Phase 1 study testing LITT + Pembrolizumab in people with Melanoma and Non-small Cell Lung Carcinoma (NSCLC), run by University of Florida at 2 sites in United States.
Trial summary
This is an open-label, historically controlled pilot study investigating the immune effect of Laser Interstitial ThermotHerapy (LITT)+ pembrolizumab in adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis after prior stereotactic… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Melanoma, Non-small Cell Lung Carcinoma (NSCLC), Renal Cell Carcinoma (RCC)
- What is being tested?
- LITT + Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 Jan 2020to 1 Dec 2023
- Phase
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic confirmation of primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor
- At least one metastatic lesion has had prior SRS. Each patient's scan must be reviewed by a neurosurgeon or radiation oncologist prior to enrollment.
- KPS ≥ 70.
- 18 years or older.
- Adequate bone marrow and organ function as defined below:
- ANC ≥ 1,500/mcL
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- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (transfusion is allowed)
- Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine > 1.5 x IULN
- Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin
- 1.5 x IULN f) AST (SGOT) and ALT (SGPT) ≤ 3 x IULN
- Candidate for pembrolizumab treatment.
- Candidate for LITT treatment:
- Metastatic lesions individually measuring 3.5 cm or less
- Only lesions that are growing or new will be treated with LITT
- Five (5) or less target metastatic lesions that are new or growing
- Lesions accessible with a laser probe as determined by the neurosurgeon performing the procedure
- Patient able to undergo MRI scans (no incompatible MRI hardware, etc.)
- A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively, within 30 days prior to study enrollment.
- Participants of childbearing age must use effective contraception:
- Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Refer to Section 9.3 for guidance on highly effective contraceptive methods.
- WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or oophorectomy) or who is not post-menopausal. Post-menopause is defined as:
- Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or (2) For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
- Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.
- 10. Ability of the patient to understand and willingness to sign an IRB approved written informed consent document.
- 11. Steroid dose equivalent to dexamethasone dose of ≤ 6mg daily at the time of enrollment.
Who cannot join
- Actively participating in another clinical trial on active study treatment; follow-up or observational status is acceptable if more than 2 weeks since last study treatment.
- History of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (with the exception of daily dexamethasone ≤ 6 mg).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that will no resolve prior to delivery of treatment (LITT), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of active autoimmune disease requiring systemic treatment within 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. (Note that prior autoimmune diseases at Grade 1 or 2 per CTCAE v. 4.0 - in the last 2 years that were deemed related to prior use of immunotherapy, will be allowed under this protocol, provided that continuation or subsequent resumption of immunotherapy, regardless of whether systemic treatment had been given, did not result in worsening of signs and symptoms of the aforementioned autoimmune diseases).
- Pneumonitis within the past 3 years (Note that patients with a history of pneumonitis in the past 3 years that was not aggravated by immunotherapy including immune checkpoint inhibitors or that has clinically resolved or improved and has not recurred or progressed clinically with subsequent immunotherapy including immune checkpoint inhibitors are eligible to participate in the study).
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test at screening.
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- Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 24 weeks after the last dose of study drug.
- Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected) infection.
- Known history of active TB (bacillus tuberculosis).
- Known history of HIV (HIV 1/2 antibodies).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
McKnight Brain Institute of the University of Florida
Gainesville, Florida, 32611
University of Florida Health
Jacksonville, Florida, 32209
About this study
Official title: Recurrent Brain Metastasis Immune Effects and RespOnse to Laser Interstitial ThermotHerapy (LITT) and Pembrolizumab in Combination (TORCH)
This is an open-label, historically controlled pilot study investigating the immune effect of Laser Interstitial ThermotHerapy (LITT)+ pembrolizumab in adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis after prior stereotactic radiosurgery (SRS).
Read the detailed description
Adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis that have failed stereotactic radiosurgery treatment will be screened. They will sign consent and complete screening procedures. Each patient will be scheduled to undergo biopsy and LITT treatment. Within two weeks of surgery, patients will begin receiving pembrolizumab every three weeks. Pembrolizumab infusions will continue until brain met recurrence per RANO for Brain Mets or up to two years, whichever comes first. Blood samples will be collected for immune monitoring. Tumor tissue will be collected for immune and genomic studies. Approximately 21 patients will be enrolled to accrue 15 evaluable subjects. Patients will be followed for survival data for one year or until death, whichever comes first.
- Conditions
- Melanoma, Non-small Cell Lung Carcinoma (NSCLC), Renal Cell Carcinoma (RCC), Small-cell Lung Cancer, Head and Neck Squamous Cell Cancer, Classical Hodgkin Lymphoma
- Being tested
- LITT + Pembrolizumab
- Keywords
- Recurrent brain metastases
- Medical subject headings
- Melanoma, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Small Cell Lung Carcinoma, Carcinoma, Transitional Cell, Stomach Neoplasms, Esophageal Neoplasms, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LITT + PembrolizumabCombination product
Also called NeuroBlate System, Keytruda
Each patient will undergo brain biopsy and laser interstitial thermotherapy (LITT). As soon as possible, no later than two weeks after LITT, pembrolizumab will be administered via infusion and continue q3wks for up to two years.
| Study group | Role | What they receive |
|---|---|---|
| Patients with Recurrent Brain Metastes | Experimental | Adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis that have failed SRS treatment will receive LITT per standard of care in combination with Pembrolizumab 200mg IV every 3 weeks (+/-3 days) up to 2 years. Receives: Combination Product: LITT + Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune Effect of LITT plus pembrolizumab
Immune profile of peripheral blood mononuclear cells (PBMCs) as measured by RNA sequencing; analysis will be performed through serial blood draws and will compare each analysis to the patient's baseline prior to treatment.
Measured: From first dose pembro through 30 days after administration of pembro
Secondary outcomes (1)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) of LITT plus pembrolizumab
Adverse events will be collected for each patient from the first dose of pembrolizumab until end of the study treatment.
Measured: From first dose pembro to 30 days post final pembro dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2019
- Study start10 Jan 2020
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
Why it stopped: Sponsor terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Monteris Medical
- Responsible party
- Sponsor
- Investigators
- Maryam Rahman, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04187872
- Sponsor's protocol ID
- IRB201902411
- Other IDs
- OCR26353
- Acronym
- TORCH
- Status last verified
- Dec 2023
- First submitted
- 3 Dec 2019
- Last updated
- 27 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Recurrent Brain Metastasis Immune Effects and RespOnse to Laser Interstitial ThermotHerapy (LITT) and Pembrolizumab in Combination (TORCH)
- ClinicalTrials.gov ID
- NCT04187872
- Acronym / sponsor ID
- TORCH / IRB201902411
- Conditions
- Melanoma, Non-small Cell Lung Carcinoma (NSCLC), Renal Cell Carcinoma (RCC), Small-cell Lung Cancer, Head and Neck Squamous Cell Cancer, Classical Hodgkin Lymphoma
- Keywords
- Recurrent brain metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor terminated
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Monteris Medical
- Study start
- 10 Jan 2020 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 5 Dec 2019 (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 an open-label, historically controlled pilot study investigating the immune effect of Laser Interstitial ThermotHerapy (LITT)+ pembrolizumab in adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis after prior stereotactic radiosurgery (SRS).
Detailed description
Adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis that have failed stereotactic radiosurgery treatment will be screened. They will sign consent and complete screening procedures. Each patient will be scheduled to undergo biopsy and LITT treatment. Within two weeks of surgery, patients will begin receiving pembrolizumab every three weeks. Pembrolizumab infusions will continue until brain met recurrence per RANO for Brain Mets or up to two years, whichever comes first. Blood samples will be collected for immune monitoring. Tumor tissue will be collected for immune and genomic studies. Approximately 21 patients will be enrolled to accrue 15 evaluable subjects. Patients will be followed for survival data for one year or until death, whichever comes first.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with Recurrent Brain Metastes | Experimental | Combination Product: LITT + PembrolizumabAdult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis that have failed SRS treatment will receive LITT per standard of care in combination with Pembrolizumab 200mg IV every 3 weeks (+/-3 days) up to 2 years. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Histologic confirmation of primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor
- At least one metastatic lesion has had prior SRS. Each patient's scan must be reviewed by a neurosurgeon or radiation oncologist prior to enrollment.
- KPS ≥ 70.
- 18 years or older.
- Adequate bone marrow and organ function as defined below:
Key exclusion criteria (10 listed)
- Actively participating in another clinical trial on active study treatment; follow-up or observational status is acceptable if more than 2 weeks since last study treatment.
- History of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (with the exception of daily dexamethasone ≤ 6 mg).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that will no resolve prior to delivery of treatment (LITT), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of active autoimmune disease requiring systemic treatment within 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. (Note that prior autoimmune diseases at Grade 1 or 2 per CTCAE v. 4.0 - in the last 2 years that were deemed related to prior use of immunotherapy, will be allowed under this protocol, provided that continuation or subsequent resumption of immunotherapy, regardless of whether systemic treatment had been given, did not result in worsening of signs and symptoms of the aforementioned autoimmune diseases).
- Pneumonitis within the past 3 years (Note that patients with a history of pneumonitis in the past 3 years that was not aggravated by immunotherapy including immune checkpoint inhibitors or that has clinically resolved or improved and has not recurred or progressed clinically with subsequent immunotherapy including immune checkpoint inhibitors are eligible to participate in the study).
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 |
|---|---|---|
| LITT + PembrolizumabAlso: NeuroBlate System, KeytrudaEach patient will undergo brain biopsy and laser interstitial thermotherapy (LITT). As soon as possible, no later than two weeks after LITT, pembrolizumab will be administered via infusion and continue q3wks for up to two years. | Combination product | Patients with Recurrent Brain Metastes |
Primary outcome
Immune Effect of LITT plus pembrolizumab
Time frame: From first dose pembro through 30 days after administration of pembro
Immune profile of peripheral blood mononuclear cells (PBMCs) as measured by RNA sequencing; analysis will be performed through serial blood draws and will compare each analysis to the patient's baseline prior to treatment.
1 secondary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) of LITT plus pembrolizumab
Time frame: From first dose pembro to 30 days post final pembro dose
Results and safety
The study was stopped early (reason given: Sponsor terminated). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2023.
- Individual participant dataSharing planned: No
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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.
Maryam Rahman, MD principal investigator
University of Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LITT + Pembrolizumab in people with Melanoma and Non-small Cell Lung Carcinoma (NSCLC), run by University of Florida at 2 sites 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 26 inclusion and 10 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 27 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
The study was stopped early (reason given: Sponsor terminated). 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?
Immune Effect of LITT plus pembrolizumab (time frame: From first dose pembro through 30 days after administration of pembro). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Dec 2023.