Clinical trial · Interventional
A Comparison of Continuous Bevacizumab (Avastin) Treatment or Placebo in Addition to Lomustine Followed by Standard of Care After Disease Progression in Participants With Glioblastoma
A Double-Blind, Placebo-Controlled, Randomised, Phase II Study Evaluating the Efficacy and Safety of Addition of Continuous Multiple Line Bevacizumab Treatment to Lomustine in Second (2nd)-Line Followed by Standard of Care (SOC) in Third (3rd)-Line and Beyond Compared to Addition of Placebo, Following First Progression of Disease (PD1) in Patients With Glioblastoma (GBM) After First (1st)-Line Treatment With Radiotherapy, Temozolomide and Bevacizumab
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This multicenter, double-blind, placebo-controlled, randomized study will evaluate the efficacy and safety of the addition of bevacizumab treatment to lomustine (in 2nd-line \[2L\] treatment) and SOC (in 3rd-line \[3L\] and subsequent lines of treatment) following first-line disease progression (PD1) in participants with newly diagnosed glioblastoma. All enrolled participants will receive 1L treatment with radiotherapy, temozolomide, and bevacizumab. At PD1, eligible participants will be randomized (1:1) to receive 2L treatment with either bevacizumab plus lomustine or placebo plus lomustine. After second-line disease progression (PD2), participants will receive 3L treatment and will continue blinded bevacizumab or placebo with the addition of an SOC agent. Following third-line disease progression (PD3), participants will receive subsequent lines of treatment and will either continue blinded bevacizumab or placebo (at the discretion of the investigator), or switch to open-label bevacizumab (at the choice of the participant).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Glioblastoma | Glioblastoma | CURATED_BROADER | 0.80 |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Bevacizumab | Drug | Bevacizumab | ALIAS |
| Lomustine | Drug | Lomustine | ALIAS |
| Placebo | Drug | — | UNRESOLVED |
| Radiotherapy | Radiation | — | UNRESOLVED |
| SOC Agent | Drug | — | UNRESOLVED |
| Temozolomide | Drug | Temozolomide | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- First-Line Bevacizumab followed by Bevacizumab + Lomustine/SOC
- description
- Participants will receive first-line treatment with radiotherapy, temozolomide, and bevacizumab. All three treatments will be given concurrently for the first 6 weeks, followed by 6 cycles (28 days each) of temozolomide plus bevacizumab, followed by bevacizumab monotherapy until PD1 or unacceptable toxicity. At PD1, participants randomized to bevacizumab will receive bevacizumab plus lomustine until PD2. Following PD2, participants will continue with blinded bevacizumab with the addition of appropriate SOC. Following PD3, for subsequent treatment lines blinded bevacizumab may continue or open-label bevacizumab may be given at the discretion of the investigator and the participant.
- interventionNames
- Drug: Bevacizumab
- Drug: Lomustine
- Radiation: Radiotherapy
- Drug: Temozolomide
- Drug: SOC Agent
- type
- PLACEBO_COMPARATOR
- label
- First-Line Bevacizumab followed by Placebo + Lomustine/SOC
- description
- Participants will receive first-line treatment with radiotherapy, temozolomide, and bevacizumab. All three treatments will be given concurrently for the first 6 weeks, followed by 6 cycles (28 days each) of temozolomide plus bevacizumab, followed by bevacizumab monotherapy until PD1 or unacceptable toxicity. At PD1, participants randomized to placebo will receive placebo plus lomustine until PD2. Following PD2, participants will continue with blinded placebo with the addition of appropriate SOC. Following PD3, for subsequent treatment lines blinded bevacizumab may continue or open-label bevacizumab may be given at the discretion of the investigator and the participant.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria at Enrollment (before PD1): * Newly diagnosed, histologically confirmed glioblastoma not previously treated with chemotherapy or radiotherapy * If female and not postmenopausal (less than \[\<\] 12 months of amenorrhea) or surgically sterile, must agree to use a highly effective contraceptive method during the treatment period and for at least 6 months after the last dose of study drug * Karnofsky performance status (KPS) greater than or equal to (\>/=) 60 * Mandatory tissue collection during pre-study surgery or biopsy for confirmation of the diagnosis and pathology * Craniotomy or intracranial biopsy site must be adequately healed. Study treatment should be initiated \> 28 days following the last surgical procedure Inclusion Criteria at Randomization (following PD1): * Documented PD1 according to RANO criteria * Eligibility for second-line treatment with lomustine and bevacizumab as investigational medicinal products * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Bevacizumab well tolerated and not interrupted for longer than 60 days during first-line treatment * Tissue submission among participants for whom operation/re-operation is indicated before second-line treatment starts; operation/re-operation performed \>/=28 days after last bevacizumab administration and second-line treatment initiated \>/=28 days after surgical wound healed * Randomization within 28 days after PD1 among participants for whom operation/re-operation is not necessary * First administration of second-line treatment no later than 2 days from randomization Exclusion Criteria at Enrollment (before PD1): * Any prior chemotherapy for glioblastoma and low-grade astrocytomas * Any prior radiotherapy to the brain or prior radiotherapy resulting in a potential overlap in the radiation field * Prior or current anti-angiogenic treatment * Treatment with any other investigational drug within 28 days or 2 investigational agent half-lives (whichever is longer) prior to first study treatment * Inadequate hematological, renal, or liver function * Inadequately controlled hypertension * Prior history of gastrointestinal perforation or abscess * Clinically significant cardiovascular disease * History or evidence of central nervous system disease unrelated to cancer unless adequately treated with standard medical therapy * History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding * Serious non-healing wound, active ulcer, or untreated bone fracture * Known hypersensitivity to any component of bevacizumab/placebo or any of the study drugs * Active infection requiring IV antibiotics at start of study treatment * Other malignancy within 5 years prior to study enrollment, except for carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ treated with curative intent * Pregnant or lactating women * Participation in any other study
References
Publications (2)
- DERIVEDBrandes AA, Gil-Gil M, Saran F, Carpentier AF, Nowak AK, Mason W, Zagonel V, Dubois F, Finocchiaro G, Fountzilas G, Cernea DM, Chinot O, Anghel R, Ghiringhelli F, Beauchesne P, Lombardi G, Franceschi E, Makrutzki M, Mpofu C, Urban HJ, Pichler J. A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma. Oncologist. 2019 Apr;24(4):521-528. doi: 10.1634/theoncologist.2018-0290. Epub 2018 Sep 28. PMID 30266892
- DERIVEDBrandes AA, Mason W, Pichler J, Nowak AK, Gil M, Saran F, Revil C, Lutiger B, Carpentier AF. Can bevacizumab prolong survival for glioblastoma patients through multiple lines of therapy? Future Oncol. 2014 May;10(7):1137-45. doi: 10.2217/fon.14.75. PMID 24947255