Lenvatinib, Pembrolizumab, and Tumor Treating Fields (TTFields) for Second-line Treatment of Glioblastoma

NCT05973903 | Withdrawn Phase 1

• 1 other identifier: 0489-22 TLV
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

GBM

Outcome Measures

Primary Outcomes (1)

• 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%.

  6 months

Study Arms (1)

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.

Drug: Lenvatinib; Drug: Pembrolizumab; Device: Tumor Treating Fields (TTFields)

Interventions

Lenvatinib DRUG

Oral Lenvatinib 20 mg once daily

Also known as: LENVIMA®, KISPLYX®

Single Arm

Pembrolizumab DRUG

intravenous pembrolizumab 200 mg every three weeks

Also known as: Keytruda

Single Arm

Tumor Treating Fields (TTFields) DEVICE

TTF extra-dermal scalp electrodes

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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).
• 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.
• 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.

Sponsors & Collaborators

• Tel Aviv Medical Center: lead

MeSH Terms

Interventions

lenvatinib; pembrolizumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neuro-Oncology Tel-Aviv Sourasky Medical Center

Model Details: Forty-seven patients will be included in the study: 10 patients as "lead-in" (phase I) and 37 patients in phase II.

Study Record Dates

• First Submitted: July 20, 2023
• First Posted: August 3, 2023
• Study Start: June 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share