GBMPhase 1/2NCT05973903
Lenvatinib, Pembrolizumab, and Tumor Treating Fields (TTFields) for Second-line Treatment of Glioblastoma
A Phase 1/2 study testing Lenvatinib, Pembrolizumab and Tumor Treating Fields (TTFields) in people with GBM, run by Tel Aviv Medical Center.
Trial summary
This will be a prospective, open label, single center, phase I lead-in study of 10 patients to a single arm phase-II study of 37 additional patients to assess the effectiveness of pembrolizumab and lenvatinib combination therapy for recurrent glioblastoma (rGBM) patients wearing TTFields electrodes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GBM
- What is being tested?
- Lenvatinib, Pembrolizumab and Tumor Treating Fields (TTFields)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2024to 1 Oct 2027
- Phase
- Phase 1/2
- 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
- The participant (or legally acceptable representative if applicable) provided written informed consent for the trial.
- Males and females at least 18 years of age on the day of signing informed consent with histopathologic evidence of GBM (from original or recurrent diagnosis) and MRI-confirmed diagnosis of rGBM.
- Have received front-line treatment (chemo-radiation with temozolomide with or without adjuvant monthly temozolomide, with or without TTF with first line therapy) per local standard of care or treatment guideline following the primary surgery with radiologically documented disease recurrence after first-line therapy.
- Wears TTFields electrodes or is suitable for wearing TTFields electrodes.
- A predicted life expectancy of >3 months.
- Have Karnofsky Performance Status (KPS) ≥70% (ECOG 0-1).
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- A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days (corresponding to the time needed to eliminate any study treatments) after the last dose of study treatment and refrain from donating sperm during this period.
- A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
- A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatments) after the last dose of study treatment.
- Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of the tumor lesion.
- Note: Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
- Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
- Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before the first dose of study treatment.
- Have adequate organ function as defined in Table 1 below. Specimens must be collected within 10 days prior to the start of study treatment
Who cannot join
- Has an implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain.
- Has evidence of increased intracranial pressure (midline shift >5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness).
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to enrollment (see Appendix 3) as documented by a positive beta-human chorionic gonadotropin [Beta-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of Beta-hCG [or hCG]). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- Is pregnant or breastfeeding at Screening or Baseline or expecting to conceive within the projected duration of the study, starting with the 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 or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) in the last 6 months (6 months are calculated from the last dose until study initiation).
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- Has received prior systemic anti-cancer therapy mAb, chemotherapy or targeted small molecule therapy within 4 weeks prior to the planned first dose of the study, including investigational agents within 4 weeks. For tyrosine kinase inhibitors (TKIs) and hormonal therapy a shorter interval of 5 half-lives is allowed between prior therapy and study treatment initiation.
- Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
- Note: If the participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. Do not administer lenvatinib for at least 2 weeks following major surgery and until adequate wound healing.
- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, and not have had radiation pneumonitis.
- Had prior grade 3 immune-related toxicity due to immune checkpoint inhibitors or non-infectious pneumonitis.
- Has a history of active tumor bleeding one month before study enrollment.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Note: mRNA vaccination for SARS-CoV-2 is not an exclusion.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. (Note: subjects who participated in local TTF study #0412-08 [A prospective, multi-center trial of NovoTTF-100A together with temozolomide (TMZ) compared to TMZ alone in patients with newly diagnosed glioblastoma (GBM)] and are in follow-up may be eligible for the current study). Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 2 mg daily dexamethasone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Note: The use of physiologic doses of corticosteroids is allowed.
- Has a known active second/additional malignancy that is progressing or has required active treatment within the past 5 years Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or lenvatinib and/or any of their excipients.
- Has an 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).
- Note: 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 an active infection requiring systemic therapy.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has a known history of human immunodeficiency virus (HIV 1/2 antibodies).
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as detected qualitative HCV RNA) infection.
- Note: no testing for hepatitis B and hepatitis C is required unless a known history of infectious hepatitis is reported.
- The participant has a known history of active Bacillus Tuberculosis (TB).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, 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.
- Has had an active allogenic tissue/solid organ transplant.
- Has uncontrolled blood pressure (Systolic BP>150 mmHg or diastolic BP>90 mmHg) despite an optimized regimen of antihypertensive medication during 7 days prior to starting study treatment, or the participant has adequately-controlled blood pressure but has had a change in antihypertensive medications within 7 days before the first dose of study treatment.
- Has clinically significant electrolyte abnormalities that have not been corrected.
- Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction (MI) or cerebrovascular accident (CVA) within 6 months of the first dose of study drug, or cardiac arrhythmia associated with hemodynamic instability requiring medical treatment at Screening.
- Has bleeding or thrombotic disorders, radiographic evidence of major blood vessel invasion/infiltration, or is at risk for severe hemorrhage.
- Note: The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
- Has >1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours.
- Has prolongation of QTc interval to >480 ms.
- Has left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
- Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
- Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
- Has a known intolerance to the study treatment (or any of its excipients).
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About this study
This will be a prospective, open label, single center, phase I lead-in study of 10 patients to a single arm phase-II study of 37 additional patients to assess the effectiveness of pembrolizumab and lenvatinib combination therapy for recurrent glioblastoma (rGBM) patients wearing TTFields electrodes.
Read the detailed description
Male and female patients, 18 years of age or older, with confirmed GBM progressed after first-line treatment. Patients either with or without first-line TTFields alternating field therapy - will be eligible to enroll in the study.
- Conditions
- GBM
- Being tested
- Lenvatinib, Pembrolizumab, Tumor Treating Fields (TTFields)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called LENVIMA®, KISPLYX®
Oral Lenvatinib 20 mg once daily
PembrolizumabDrug
Also called Keytruda
intravenous pembrolizumab 200 mg every three weeks
Tumor Treating Fields (TTFields)Device
TTF extra-dermal scalp electrodes
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Single-arm: participants will be treated with TTFields (200 kHz) + intravenous pembrolizumab 200 mg every three weeks and oral lenvatinib 20 mg once daily until evident progressive disease by Response Assessment in Neuro-Oncology (RANO) criteria, unacceptable toxicity, withdrawal of consent, or until completion of 35 treatment cycles (approximately 2 years) with pembrolizumab. Participants who complete treatment with pembrolizumab after 35 cycles (approximately 2 years) or CR will continue to receive lenvatinib and TTF until disease progression, development of unacceptable toxicity, or withdrawal of consent. Receives: Drug: Lenvatinib; Drug: Pembrolizumab; Device: Tumor Treating Fields (TTFields) |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression free survival (PFS-6)
Treatment with pembrolizumab and lenvatinib in rGBM patients wearing TTFields electrodes is expected to increase PFS-6 from 15 to 30%.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2023
- Study start1 Jun 2024
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Oct 2027 (estimated)
Why it stopped: It was decided by the researcher not to open the study due to administrative issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GBMStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Forty-seven patients will be included in the study: 10 patients as "lead-in" (phase I) and 37 patients in phase II.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tel Aviv Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deborah T. Blumenthal, MD, Tel Aviv Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05973903
- Sponsor's protocol ID
- 0489-22 TLV
- Status last verified
- Dec 2024
- First submitted
- 20 Jul 2023
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lenvatinib, Pembrolizumab, and Tumor Treating Fields (TTFields) for Second-line Treatment of Glioblastoma
- ClinicalTrials.gov ID
- NCT05973903
- Acronym / sponsor ID
- 0489-22 TLV
- Conditions
- GBM
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: It was decided by the researcher not to open the study due to administrative issues.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Tel Aviv Medical CenterUniversity, hospital or other
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 3 Aug 2023 (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 will be a prospective, open label, single center, phase I lead-in study of 10 patients to a single arm phase-II study of 37 additional patients to assess the effectiveness of pembrolizumab and lenvatinib combination therapy for recurrent glioblastoma (rGBM) patients wearing TTFields electrodes.
Detailed description
Male and female patients, 18 years of age or older, with confirmed GBM progressed after first-line treatment. Patients either with or without first-line TTFields alternating field therapy - will be eligible to enroll in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Forty-seven patients will be included in the study: 10 patients as "lead-in" (phase I) and 37 patients in phase II.
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Lenvatinib, Drug: Pembrolizumab, Device: Tumor Treating Fields (TTFields)Single-arm: participants will be treated with TTFields (200 kHz) + intravenous pembrolizumab 200 mg every three weeks and oral lenvatinib 20 mg once daily until evident progressive disease by Response Assessment in Neuro-Oncology (RANO) criteria, unacceptable toxicity, withdrawal of consent, or until completion of 35 treatment cycles (approximately 2 years) with pembrolizumab. Participants who complete treatment with pembrolizumab after 35 cycles (approximately 2 years) or CR will continue to receive lenvatinib and TTF until disease progression, development of unacceptable toxicity, or withdrawal of consent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- The participant (or legally acceptable representative if applicable) provided written informed consent for the trial.
- Males and females at least 18 years of age on the day of signing informed consent with histopathologic evidence of GBM (from original or recurrent diagnosis) and MRI-confirmed diagnosis of rGBM.
- Have received front-line treatment (chemo-radiation with temozolomide with or without adjuvant monthly temozolomide, with or without TTF with first line therapy) per local standard of care or treatment guideline following the primary surgery with radiologically documented disease recurrence after first-line therapy.
- Wears TTFields electrodes or is suitable for wearing TTFields electrodes.
- A predicted life expectancy of >3 months.
Key exclusion criteria (41 listed)
- Has an implanted pacemaker, defibrillator, deep brain stimulator, other implanted electronic devices in the brain.
- Has evidence of increased intracranial pressure (midline shift >5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness).
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to enrollment (see Appendix 3) as documented by a positive beta-human chorionic gonadotropin [Beta-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of Beta-hCG [or hCG]). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- Is pregnant or breastfeeding at Screening or Baseline or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
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 |
|---|---|---|
| LenvatinibAlso: LENVIMA®, KISPLYX®Oral Lenvatinib 20 mg once daily | Drug | Single Arm |
| PembrolizumabAlso: Keytrudaintravenous pembrolizumab 200 mg every three weeks | Drug | Single Arm |
| Tumor Treating Fields (TTFields)TTF extra-dermal scalp electrodes | Device | Single Arm |
Primary outcome
progression free survival (PFS-6)
Time frame: 6 months
Treatment with pembrolizumab and lenvatinib in rGBM patients wearing TTFields electrodes is expected to increase PFS-6 from 15 to 30%.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lenvatinib, Pembrolizumab and Tumor Treating Fields (TTFields) in people with GBM, run by Tel Aviv Medical Center.
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 15 inclusion and 41 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: withdrawn, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 withdrawn before enrolling participants, so there are no results.
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?
progression free survival (PFS-6) (time frame: 6 months). 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 4 Dec 2024.