Summary

Eligibility
for people ages 18-130 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

This study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AZD9574 individually and in combination with anti-cancer agents in patients with advanced cancer that has recurred/progressed.

Official Title

A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (CERTIS1)

Details

This is a modular phase I/IIa, multi-centre, multi-part, open-label, dose escalation, and dose expansion study. Approximately 255 participants will be enrolled and assigned to study treatments. This study consists of individual modules each evaluating safety and tolerability. - Core protocol which contains information applicable to all modules. - Module 1 (AZD9574 monotherapy): - Part A (dose-escalation cohorts) will include participants with advanced/relapsed ovarian, breast, pancreatic or prostate cancer that are deemed suitable for a Poly ADP-Ribose Polymerase (PARPi) by the Investigator. - Part B (dose-expansion cohorts): - Cohort B1 will include participants with advanced/relapsed Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer participants with BRCA mutated (BRCA1m, and BRCA2m), PALB2 mutation (PALB2m), RAD51Cm or RAD51Dm, without evidence of brain metastasis at baseline Magnetic Resonance Imaging (MRI) scan. - Cohort B2 will include participants with advanced/relapsed HER2-negative breast cancer participants with BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm, who have either untreated or treated brain metastases that are not requiring immediate local therapy. - Module 2 (AZD9574 in combination with temozolomide (TMZ): - Part A (dose-escalation cohorts) will include participants with Isocitrate Dehydrogenase (IDH)-mutant glioma. - Dose expansion for Module 2 may be added in the future following a protocol amendment.

Keywords

Advanced Solid Malignancies, CERTIS1, Poly ADP-ribose Polymerase inhibitor (PARPi), Anti-tumour, Breast cancer, Ovarian cancer, Fallopian tube cancer, Prostate cancer, Pancreatic cancer, Soft tissue disease, Glioma, Astrocytoma, Oliogodendroglioma, Neoplasms, Temozolomide, AZD9574

Eligibility

You can join if…

Open to people ages 18-130

  • Eastern Cooperative Oncology Group performance status (ECOG PS) with no deterioration over the previous 2 weeks.
  • Progressive cancer at the time of study entry.
  • Non-sterilised male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to approximately 3 months after the last dose of study intervention.
  • Adequate organ and marrow function.

Module 1:

  • Female participants of childbearing potential must have a negative pregnancy test result at screening and prior to each cycle administration of AZD9574.

Part A:

  • Participants must have one of the following:

(i) Histologically or cytologically confirmed relapsed advanced ovarian, fallopian tube or primary peritoneal cancer and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or RAD51D (ii) Histologically or cytologically confirmed HER2-negative carcinoma of the breast with recurrent locally advanced or metastatic disease and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D. (iii) Histologically or cytologically confirmed advanced/metastatic castration-resistant prostate cancer (CRPC) and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D (d) Histologically or cytologically confirmed advanced/metastatic pancreatic cancer and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.

  • Participants must have evaluable disease.
  • Patients must be suitable for treatment with a PARPi.

Part B:

  • Participants must have metastatic or recurrent locally advanced histologically or cytologically confirmed Human Epidermal growth factor Receptor 2 (HER2)-negative carcinoma of the breast and evidence of a predicted loss of function germline or tumour mutation.
  • Participants must have at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter.
  • Participants who have received platinum chemotherapy for advanced breast cancer are eligible to enter the study provided there has been no evidence of disease progression during the platinum chemotherapy.
  • Participants who have received prior platinum-based chemotherapy as neo-adjuvant/adjuvant treatment are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and first dose of study intervention.

Module 2:

  • Participants must be suitable for treatment with TMZ.
  • Participants must have IDH1/2-mutant glioma.
  • Participants should have progressive disease after prior radiation therapy and one prior line of alkylating chemotherapy for their disease.
  • Recurrent disease must be evaluable by MRI.
  • Female participants of childbearing potential must have a negative pregnancy test result at screening and prior to each cycle administration of AZD9574 and TMZ.
  • Adequate organ and marrow function.

You CAN'T join if...

  • Major surgery within 4 weeks of the first dose of study intervention.
  • Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study intervention.
  • With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study intervention.
  • Any known history of persisting severe pancytopenia due to any cause.
  • Spinal cord compression unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study intervention.
  • History of uncontrolled seizures or with need for concurrent administration of more than 2 antiepileptic drugs, or history of epileptic disorder or any seizure history unrelated to tumour.
  • History of severe brain injury or stroke.
  • Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
  • Uncontrolled intercurrent illness within the last 12 months.
  • Any known predisposition to bleeding.
  • Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9574.
  • Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
  • Known contra-indication to gadolinium-enhanced Magnetic Resonance Imaging (MRI) or, if applicable, not able to be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 7 days) prior to the baseline MRI.
  • Any concurrent anti-cancer therapy or concurrent use of prohibited medications.

Module 1:

Part A:

  • Participants that have received > one prior line of therapy in any setting with a PARPi-based regimen.
  • Participants with an INR >1.5 unless the patient is receiving non-vitamin K antagonist oral anticoagulants.
  • Participants with LMD unless the LMD is of low volume or is previously irradiated and the participant is asymptomatic from the LMD.

Part B:

  • Participants with an International Normalised Ratio (INR) >1.5 unless the patient is receiving non-vitamin K antagonist oral anticoagulants.
  • Participants with LMD are excluded unless the LMD is of low volume or is previously irradiated and the participant is asymptomatic from the LMD.

Module 2:

  • Participants who have received a PARPi previously.
  • Known hypersensitivity to TMZ or dacarbazine or known history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD9574.
  • Participants who have received > 1 prior line of alkylating chemotherapy regimen.
  • Participants who had previously experienced Grade 4 haematological toxicities or Grade 3 neutropenia associated with infections, or Grade 3 thrombocytopenia with clinically significant bleeding during prior alkylating chemotherapy.
  • Participants who have received bevacizumab within the last 6 months.
  • Not requiring continuous corticosteroids at a dose of >10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study intervention.

Locations

  • Research Site not yet accepting patients
    San Francisco California 94143 United States
  • Research Site not yet accepting patients
    Los Angeles California 90095 United States

Details

Status
accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
(estimated)
Sponsor
AstraZeneca
ID
NCT05417594
Phase
Phase 1/2 Solid Malignancies Research Study
Study Type
Interventional
Participants
Expecting 195 study participants
Last Updated