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ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas

PHASE2RECRUITING

This is a Phase II open-label study to investigate the safety and efficacy of ACT001 in patients with DIPG and H3K27-altered HGG.

Study details:

Patients will be enrolled on either Cohort A for newly diagnosed DIPG or on Cohort B for those with progressive / refractory DIPG or progressive / recurrent / refractory H3K27-altered HGG. Each cohort will receive ACT001 at 875 mg/m2 orally BID for 28 days (1 cycle of treatment), up to a maximum dose of 1700 mg BID. If patients are experiencing clinical benefit from study therapy, they will continue to receive ACT001 in repeat 28-day cycles for up to 26 cycles (approximately 2 years) or until disease progression, whichever occurs first.

Continuation of treatment beyond 26 cycles may be considered if patients are receiving clinical benefit from the study, at the discretion of the sponsor and treating physician.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
  2. Cohort A: Newly Diagnosed DIPG - Patients with newly-diagnosed DIPG with typical MRI findings (tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons) with or without biopsy and have completed radiation therapy (RT) within 28 to 35 calendar day prior to start of therapy.
  3. Patients must have started RT <42 calendar days of radiographic diagnosis (for non-biopsied DIPG patients only) or definitive surgery, whichever is later.
  4. Patients must have received RT, but no other anti-cancer therapy other than surgery, and/or steroids prior to enrollment.
  5. Cohort B: progressive/refractory/recurrent DIPG or H3K27-altered HGG - Patients with DIPG (no biopsy required) or pathologically-confirmed (at diagnosis or recurrence) extra-pontine H3K27-altered HGG who have progressive, refractory or recurrent disease following frontline treatment that included at least focal RT.
  6. Patients with refractory disease must have completed RT >6 months prior to study enrollment.
  7. Patients with progressive disease only at the primary site(s) must have completed RT more than 3 months prior to enrollment.
  8. Patients with progressive disease only at the primary site(s) who completed radiation therapy 3 to 6 months prior to enrollment must have had at least one follow up MRI to confirm progression (rather than pseudo-progression).
  9. Patients with progressive disease due to the development a new metastatic site are eligible as long as eligibility criteria 3 (disease status) and 5 (prior RT) are met.
  10. Patients with metastatic disease are eligible.
  11. Cohort A: patients may have any disease status but must have completed initial radiation therapy (RT) before enrollment.
  12. Cohort B: Patients must have measurable disease assessable by MRI imaging.
  13. Patients may have metastatic disease.
  14. Lesions irradiated within the last 6 months are not considered measurable unless they show definitive progression following RT.
  15. Karnofsky Performance Scale score ≥ 50% for patients > 16 years of age and Lansky Performance Scale score > 50% for patients ≤ 16 years of age (applies to all patients).
  16. Patients who are unable to walk because of paralysis, but who are capable of using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  17. For Cohort A ONLY: Patients must not have received any prior therapy other than surgery, radiation (focal to disease) and/or steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy).
  18. Patients must enroll and start treatment on study between 28 and 35 calendar days post-completion of RT.
  19. Patients must have started RT <42 calendar days of initial diagnosis.
  20. Radiotherapy must have been administered at standard dose of 54 Gy for DIPG patients.
  21. For Cohort B ONLY: Patients must have fully recovered from adverse events due to prior treatment with investigational or conventional agents must have recovered to a severity of Grade 0 or Grade 1.
  22. Patients with chronic Grade 2 toxicities may be eligible per discretion of the Investigator and Sponsor.
  23. The wash out period between the prior anti-cancer chemotherapy, and first dose of ACT001 must meet specific duration requirements.
  24. Patients must be ≥ 3 months since autologous stem cell transplant.
  25. Patients must sign a written informed consent.
  26. Absence of other clinically significant concomitant active medical disorder, based on the investigator's judgement.

Exclusion criteria

  1. Cohort A only: Patients with metastatic disease.
  2. Patients who are currently receiving other anti-cancer agents are not eligible.
  3. Patients who are currently receiving another investigational drug are not eligible.
  4. Patients who currently have an uncontrolled infection are not eligible.
  5. Patients who have received a prior solid organ transplantation are not eligible.
  6. Pregnant or breast-feeding women will not be entered on this study due to unknown risks.
  7. Patients of childbearing or child fathering potential must agree to use adequate contraceptive methods while being treated on this study and for 3 months after completing therapy.
  8. Patients who may not be able to comply with the safety monitoring requirements of the study are not eligible.
  9. Patients who have previously received either ACT001 or parthenolide are not eligible.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE2

trial

Study ID

NCT06838676

Intervention or treatment

DRUG: ACT001

Conditions

  • Diffuse Intrinsic Pontine Gliomas (DIPG)
  • Progressive DIPG
  • Refractory DIPG
  • Recurrent DIPG
  • H3K27-altered High Grade Glioma

  • Condition: Diffuse Intrinsic Pontine Gliomas (DIPG), Progressive DIPG and more

  • DRUG: ACT001

  • Randwick, New South Wales, Australia and more

  • Sponsor: Nationwide Children's Hospital

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Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

Sydney Children's Hospital

Select from list below to view details:

  • Sydney Children's Hospital

    Randwick, New South Wales, Australia

  • Queensland Children's Hospital

    South Brisbane, Queensland, Australia

  • Royal Children's Hospital

    Melbourne, Victoria, Australia

  • Perth Children's Hospital

    Perth, Western Australia, Australia

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Who is running the clinical trial?

NCH

Nationwide Children's Hospital

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Cohort A
  • Patients with newly-diagnosed DIPG with typical MRI findings
Drug: ACT001
    EXPERIMENTAL: Cohort B [ENROLLMENT PAUSED]
    • Patients with progressive/recurrent DIPG or H3K27-altered HGG OR refractory disease
    Drug: ACT001

      What is the study measuring?

      Primary Outcome

      MeasureDescriptionTime Frame
      Overall Survival (OS) for newly diagnosed DIPGTo assess the overall survival for newly-diagnosed patients with DIPG treated with RT followed by ACT001.From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
      Objective Response Rate (ORR) in Progressive/Refractory/Recurrent HGG after frontline RTTo assess the rate of objective response rate (defined as partial response + complete response) in patients who have been treated with at least frontline focal RT and have progressive DIPG or progressive/recurrent/refractory H3K27-altered HGG who are treated with ACT001Date on treatment through 30 days following end of protocol treatment

      Secondary Outcome

      MeasureDescriptionTime Frame
      Overall Survival in Progressive/Refractory/Recurrent DIPG and H3K27-altered DIPGTo estimate the overall survival and duration of disease control for patients who have been treated with at least RT and have progressive DIPG or progressive/recurrent/refractory H3K27-altered HGG who are treated with ACT001From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
      Claim this trial

      References

      Clinical Trials Gov: ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas

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