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RecruitingLast updated: 12 April 2024

LUMOS2: This clinical trial is evaluating a new approach to the treatment of people with lower grade glioma that has started to grow again (i.e. is recurrent) following initial treatment with chemotherapy and radiation therapyLow & Anaplastic Grade Glioma Umbrella Study of Molecular Guided TherapieS

Clinical summary

Summary

 

Eligible participants will undergo a surgical procedure to collect a tissue sample from the tumour, which will be screened for biomarkers and mutations. The results of this testing will then be used by a panel of experts who will make a treatment recommendation.

If you have a mutation that matches one of the treatment arms, this will be recommended to you. If you do not have a mutation that matches one of the treatment arms, you will be randomised (i.e. allocated by chance) to one of the treatments that does not require a matching mutation.

The study treatments available include:

  • Arm 1 - the oral medication Paxalisib administered once daily
  • Arm 2 - the intravenous infusion AK104 administered once every two weeks
  • Arm 3 - the oral medication Selinexor administered once daily.

Treatment will continue until disease progression is documented or until participants experience intolerable toxicity or withdraw for another reason. During treatment, participants will undergo an MRI scan every 8 weeks to assess for disease progression and response to treatment, and will complete questionnaires regarding their quality of life.

It is hoped that screening tumour tissue for specific biomarkers to direct targeted treatment will be effective, safe, and cost-effective for the management of people with recurrent lower grade glioma.

Conditions

This trial is treating patients with IDH-mutant, recurrent glioma

Cancer

Brain and Spinal Cancers Brain and Spinal

Age

People18+

Phase

II

Trial Acronym

LUMOS2

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

The University of Sydney, Cooperative Trials Group for Neuro-Oncology

Scientific Title

Low & Anaplastic Grade Glioma Umbrella Study of Molecular Guided TherapieS

Eligibility

Inclusion

Molecular profiling:
1. Adults, aged 18 years and older
2. Histologically confirmed glioma, IDH-mutant, histologically grade 2 or 3 at initial diagnosis (i.e., without necrosis or microvascular proliferation); including CDKN2A/B homozygous deleted IDH-mutant astrocytomas but not IDH-wildtype diffuse astrocytomas with any of TERT promoter mutation, EGFR amplification and/or +7/-10 copy number changes (i.e., molecular features of glioblastoma).
3. Has evidence of progressive disease (defined as new contrast-enhancing tumour and/or 25% increase in the size of the T2/FLAIR area compared to prior imaging after prior treatment with radiotherapy and chemotherapy; with a clinical indication for neurosurgery).
4. Prior treatment with radiotherapy and alkylating chemotherapy, defined as either sequential therapy with CNS radiotherapy then an akylating agent, or concurrent CNS radiotherapy with an alkylating agent.
5. ECOG performance status 0-2.
6. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments; It is the intention that molecular profiling is performed for patients who are in principle wishing to take part in a treatment arm if they are found to be eligible following molecular profiling.
7. Signed, written informed consent (LUMOS2 molecular profiling and linkage to Medicare records).



Additional inclusion criteria for:
Arm 1 - Paxalisib:
1. Histologically confirmed glioma, IDH-mutant, histologically grade 2 or 3 at initial diagnosis (i.e., without necrosis or microvascular proliferation); including CDKN2A/B homozygous deleted IDH-mutant astrocytomas but not IDH-wildtype diffuse astrocytomas with any of TERT promoter mutation, EGFR amplification and/or +7/-10 copy number changes (i.e., molecular features of glioblastoma).
2. Adequate recovery from surgery in the opinion of the treating physician (as evidenced by ECOG performance status 0-2).
3. Adequate organ system function post-surgery as assessed by the following minimal laboratory requirements.
a) Bone marrow function; platelets greater than or equal to 100 x 109/L, ANC greater than or equal to 1.5 x 109/L, and haemoglobin greater than or equal to 90g/L (5.6mmol/L)
b) Liver function; ALT/AST less than or equal to 3 x ULN and total bilirubin less than or equal to 1.5xULN
c) Renal function; serum creatinine less than or equal to 1.5xULN
4. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
5. LUMOS2 Molecular Tumour Advisory Panel (MTAP) report confirming eligibility to this treatment arm.
6. Signed, written informed consent

Arm 2 - AK104:
1. Histologically confirmed glioma, IDH-mutant, histologically grade 2 or 3 at initial diagnosis (i.e., without necrosis or microvascular proliferation); including CDKN2A/B homozygous deleted IDH-mutant astrocytomas but not IDH-wildtype diffuse astrocytomas with any of TERT promoter mutation, EGFR amplification and/or +7/-10 copy number changes (i.e., molecular features of glioblastoma).
2. Adequate recovery from surgery in the opinion of the treating physician (as evidenced by ECOG performance status 0-2).
3. Adequate organ system function post-surgery as assessed by the following minimal laboratory requirements
a. Bone marrow function; platelets greater than or equal to 100 x 109/L, ANC greater than or equal to 1.5 x 109/L, and haemoglobin greater than or equal to 90g/L (5.6mmol/L).
b. Liver function; ALT/AST less than or equal to 3 x ULN and total bilirubin less than or equal to 1.5xULN.
c. Renal function; serum creatinine less than or equal to 1.5xULN.
4. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments; and
5. LUMOS2 Molecular Tumour Advisory Panel (MTAP) report confirming eligibility to this treatment arm
6. Signed, written informed consent.

Arm3 - Selinexor:
1. Histologically confirmed glioma, IDH-mutant, histologically grade 2 or 3 at initial diagnosis (i.e., without necrosis or microvascular proliferation); including CDKN2A/B homozygous deleted IDH-mutant astrocytomas but not IDH-wildtype diffuse astrocytomas with any of TERT promoter mutation, EGFR amplification and/or +7/-10 copy number changes (i.e., molecular features of glioblastoma).
2. Adequate recovery from surgery in the opinion of the treating physician (as evidenced by ECOG performance status 0-2).
3. Adequate organ system function post-surgery as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug).
a) Bone marrow function; platelets greater than or equal to 100 x 109/L, ANC greater than or equal to 1.5 x 109/L, and haemoglobin greater than or equal to 90g/L (5.6mmol/L).
b) Liver function; ALT/AST less than or equal to 3 x ULN and total bilirubin less than or equal to 1.5xULN.
c) Renal function; serum creatinine less than or equal to 1.5xULN.
4. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments; and
5. LUMOS2 Molecular Tumour Advisory Panel (MTAP) report confirming eligibility to this treatment arm
6. Signed, written informed consent.

Exclusion

 

Molecular profiling:
1. Prior treatment with bevacizumab
2. Intra-surgical treatments (e.g., oncolytic virus administration, Gliadel wafers) at their last craniotomy prior to study enrolment.
3. Comorbidities or conditions (e.g., psychiatric) that may compromise assessment of key outcomes or in the opinion of the physician limit the ability of the participant to comply with the protocol.
4. Unable (e.g., due to pacemaker or ICD device) or unwilling to have a contrast-enhanced MRI of the head
5. Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy (Those with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy))
6. Pregnancy, lactation, or inadequate contraception. Persons who are able to become pregnant, and having sexual relationships in which they may become pregnant, must use a reliable means of contraception and must have a negative pregnancy test done within 7 days prior to registration. Persons who are having sexual relationships in which their partner may become pregnant must have been surgically sterilised or use a (double if required) barrier method of contraception.

Additional exclusion criteria for:
Arm 1 - Paxalisib:
1. Intra-surgical treatments (e.g., oncolytic virus administration, Gliadel wafers) at their last craniotomy prior to study enrolment;
2. Presence of any metastatic tumours at the time of craniotomy that are not consistent with original glioma diagnosis.
3. Prior IDH inhibitor therapy within 4 weeks of first dose of LUMOS2 investigational treatment.
4. Prior investigational agents within 4 weeks of first dose of LUMOS2 investigational treatment.
5. Concomitant medications which may interact with the investigational product(s) in the opinion of the physician
6. Baseline QT interval >470msec or clinically significant cardiac history (myocardial infarction or symptomatic bradycardia, active congestive heart failure or angina pectoris).

Arm 2 - AK104:
1. Intra-surgical treatments (e.g., oncolytic virus administration, Gliadel wafers) at their last craniotomy prior to study enrolment
2. Presence of any metastatic tumours at the time of craniotomy that are not consistent with original glioma diagnosis.
3. Prior IDH inhibitor therapy within 4 weeks of first dose of LUMOS2 investigational treatment.
4. Prior investigational agents within 4 weeks of first dose of LUMOS2 investigational treatment.
5. Concomitant medications which may interact with the investigational product(s) in the opinion of the physician.
6. Clinically significant symptomatic auto-immune disease that may predispose patient to immune-related adverse events in the opinion of the treating physician.

Arm3 - Selinexor:
1. Intra-surgical treatments (e.g., oncolytic virus administration, Gliadel wafers) at their last craniotomy prior to study enrolment;
2. Presence of any metastatic tumours at the time of craniotomy that are not consistent with original glioma diagnosis.
3. Prior IDH inhibitor therapy within 4 weeks of first dose of LUMOS2 investigational treatment.
4. Prior investigational agents within 4 weeks of first dose of LUMOS2 investigational treatment.
5. Concomitant medications which may interact with the investigational product(s) in the opinion of the physician.

Inclusion

  • You have had a certain type of treatment or surgical procedure.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had treatment, but your cancer has come back.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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