Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies
a study on Solid Malignancies Neoplasms
Summary
- Eligibility
- for people ages 18-130 (full criteria)
- Location
- at UCLA UCSF
- Dates
- study startedestimated 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
Los Angeles California 90095 United States - Research Site
not yet accepting patients
San Francisco California 94143 United States - Research Site
not yet accepting patients
La Jolla California 92093 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 research study
- Study Type
- Interventional
- Participants
- Expecting 195 study participants
- Last Updated