Overview
Bevacizumab and ICIs + hSRT in Symptomatic Melanoma Brain Metastases
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2026-01-30
2026-01-30
Target enrollment:
0
0
Participant gender:
All
All
Summary
Single arm phase I/II trial to evaluate the safety and efficacy of the combination of bevacizumab, with ipilimumab plus nivolumab, and hypofractionated stereotactic radiotherapy (hSRT) in patients with symptomatic melanoma brain metastases (MBM).Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Melanoma and Skin Cancer Trials LimitedTreatments:
Bevacizumab
Ipilimumab
Nivolumab
Criteria
Inclusion Criteria:- 1. Histologically (or cytologically) proven metastatic melanoma, with radiologically
confirmed brain metastases.
- 2. Symptomatic from brain metastases at the time of study enrolment, or brain
metastases that requires corticosteroids for the management of neurological symptoms.
- 3. Intracranial lesions amenable to hypofractionated stereotactic radiotherapy. These
are defined as all intracranial melanoma lesions greater or equal to 5 mm in diameter,
all intracranial lesions that are causing symptoms, and all intracranial lesions
located in the eloquent areas of the brain.
- 4. World Health Organisation (WHO) performance status of 0 - 2
- 5. At least one brain metastasis has to be symptomatic.
- 6. Laboratory tests required: Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥
1 x 109/L Platelet count ≥ 100 x 109/L Either: Serum bilirubin ≤ 1.5 x upper limit of
normal (ULN) (Patients with isolated hyperbilirubinaemia due to Gilbert's syndrome are
allowed.) Or: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x
(ULN) unless raised due to tumour in which case up to 5 x ULN is permissible
Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault or MDRD are acceptable)
- 7. Age ≥ 18 years
- 8. Able to provide informed written consent (signed and dated), attend trial site for
study visits and be capable of co-operating with treatment and follow-up
Exclusion Criteria:
- 1. Prior radiotherapy to the brain
- 2. Active concurrent malignancy requiring systemic anti-cancer therapy within the last
2 years. Patients with any malignancy treated with curative intent and no evidence of
disease will be eligible for this trial.
- 3. Prior systemic therapy for melanoma, unless given in the neoadjuvant or adjuvant
setting for extracranial disease only, completed more than >6 months prior to
enrolment in this trial and if administered with radiological proof of the absence of
brain metastases
- 4. Inability to undergo MRI of the brain
- 5. Definitive leptomeningeal disease. Patients with equivocal leptomeningeal disease
may be included on the trial after discussion with CPI.
- 6. Female patients who are pregnant or lactating. Patients who are able to become
pregnant, must return a negative serum or urine pregnancy test before enrolment and
agree to use two forms of contraception (one effective form plus a barrier method)
[oral, injected or implanted hormonal contraception and condom; intra-uterine device
and condom; diaphragm with spermicidal gel and condom] or agree to sexual abstinence,
effective from signing the consent form, throughout the trial and for six months after
any treatment for melanoma, radiotherapy or immunotherapy, are considered eligible.
- 7. Male patients with partners of child-bearing potential (unless they agree to take
measures not to father children by using a barrier method of contraception or to
sexual abstinence effective from the first administration of bevacizumab, throughout
the trial and for six months afterwards after treatment the end-of-trial visit. Men
with partners of child-bearing potential must also be willing to ensure that their
partner uses an effective method of contraception for the same duration for example,
hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual
abstinence). Men with pregnant or lactating partners must be advised to use barrier
method contraception to prevent exposure of the foetus or neonate. Abstinence is only
considered to be an acceptable method of contraception when this is in line with the
preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar,
ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable
methods of contraception.
- 8. Haemorrhage encompassing >50% of any lesion that is >10 mm in diameter (excluding
surrounding oedema). A modern susceptibility-sensitive MRI sequence such as SWI is
mandatory.
- 9. Brain metastases greater than 5 cm in maximal diameter
- 10. Increasing corticosteroid dose for 48 hours prior to initiation of study therapy
OR current dexamethasone-equivalent dose of >8 mg per day
- 11. Major thoracic or abdominal surgery within 28 days prior to initiation of trial
treatment
- 12. Neurosurgery within 14 days prior to initiation of trial treatment
- 13. Active or history of severe auto-immune disease requiring systemic
anti-inflammatory therapy. Patients with well-controlled auto-immune diseases not
requiring systemic anti-inflammatory therapy may be included after consultation with
the CPI. Severe auto-immune respiratory disease will be excluded from the trial.
- 14. History of inflammatory bowel disease
- 15. Requirement for ongoing concurrent systemic immunosuppressive therapy (other than
corticosteroids).
- 16. History of intra-abdominal inflammatory process within 6 months prior to
initiation of trial treatment, including but not limited to peptic ulcer disease,
diverticular disease or colitis.
- 17. History of abdominal or trachea-oesophageal fistula, gastrointestinal perforation
or intra-abdominal abscess within 6 months prior to initiation of trial treatment
- 18. History of intestinal obstruction and/or clinical signs or symptoms of
gastrointestinal obstruction including sub-occlusive disease related to the underlying
disease or requirement for routine parenteral hydration, parenteral nutrition or tube
feeding within 6 months prior to initiation of trial treatment
- 19. Any Grade ≥3 haemorrhage or bleeding event within 28 days of trial treatment
initiation. Patients presenting with haemorrhagic brain metastases that have been
adequately treated with neurosurgery are not excluded under this criterion but remain
subject to criterion 12 pertaining to timing of neurosurgery.
- 20. Current use of full-dose anticoagulation or thrombolytic therapy within 10 days of
initiation of trial treatment
- 21. Evidence of bleeding diatheses or significant coagulopathy
- 22. History of inadequately controlled arterial hypertension (systolic BP ≥160 mm Hg
or diastolic BP ≥100 mm Hg despite maximal medical therapy); prior history of
hypertensive crises or hypertensive encephalopathy
- 23. Concurrent congestive heart failure, prior history of NYHA class III/ IV cardiac
disease, prior history of cardiac ischaemia or prior history of cardiac arrhythmia
- 24. Concurrent participation in another interventional clinical trial or intention to
do so. Concurrent participation in an observational trial is acceptable.
- 25. Any other condition which in the Investigator's opinion would not make the patient
a good candidate for the clinical trial.