490 Participants Needed

AZD9574 for Advanced Solid Tumors

(CERTIS1 Trial)

Recruiting at 21 trial locations
AC
AB
Overseen ByAstraZeneca Breast Cancer Study Locator Service
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial tests AZD9574, a new drug that stops cancer cells from repairing themselves. It targets patients with advanced or relapsed cancers who need new treatment options. The drug is tested alone and in combination with other cancer-fighting drugs.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that concurrent use of certain medications is prohibited, so it's best to discuss your current medications with the study team to ensure they are not among the restricted ones.

What data supports the effectiveness of the drug AZD9574 for advanced solid tumors?

Temozolomide, a component of the treatment, has shown effectiveness in treating various types of cancer, including brain tumors like glioblastoma and other cancers such as melanoma. It works by damaging the DNA of cancer cells, which can help stop their growth.12345

What safety information is available for AZD9574 (Temozolomide) in humans?

Temozolomide, also known as AZD9574, has been linked to severe blood-related side effects and a condition called myelodysplasia (a bone marrow disorder) when used long-term. It is considered potentially leukemogenic (can cause leukemia) if given in high cumulative doses.15678

How does the drug AZD9574 differ from other treatments for advanced solid tumors?

AZD9574 is unique because it combines with Temozolomide, a drug known for treating brain tumors and other cancers by damaging cancer cell DNA. This combination may offer a novel approach for advanced solid tumors, potentially enhancing the effectiveness of treatment by leveraging Temozolomide's ability to cross the blood-brain barrier and target cancer cells.12459

Eligibility Criteria

This trial is for adults with advanced solid tumors that have worsened despite previous treatments. They must be in stable condition, not planning to conceive, and have specific genetic mutations related to cancer growth. People who've had certain prior therapies or severe reactions to similar drugs, uncontrolled diseases, or are unable to take oral medications cannot join.

Inclusion Criteria

I am not breastfeeding and won't donate or use my eggs for 6 months after the study ends.
Participants must be capable of eating a high fat meal and adhering to fasting restrictions
My condition worsened after treatment for advanced cancer and I have no other good treatment options.
See 23 more

Exclusion Criteria

I have had a severe brain injury or stroke.
I cannot take AZD9574 due to severe nausea, vomiting, gut diseases, swallowing issues, or major bowel surgery.
I cannot have MRI with gadolinium or cannot keep my steroid dose stable.
See 16 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive AZD9574 as monotherapy or in combination with anti-cancer agents in dose-escalation cohorts to assess safety and tolerability.

Cycle 0 (7 days) and Cycle 1 (28 days)
Multiple visits for dose administration and monitoring

Dose Expansion

Participants are enrolled in dose-expansion cohorts to further evaluate safety, tolerability, and preliminary efficacy.

Approximately 3 years
Visits every 8 weeks for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3 years
Regular follow-up visits

Treatment Details

Interventions

  • AZD9574
  • Temozolomide
Trial OverviewThe study tests AZD9574 alone and combined with other anti-cancer agents (Trastuzumab Deruxtecan, Datopotamab Deruxtecan, Temozolomide) on 490 participants. It aims to evaluate safety and early signs of effectiveness while monitoring how the body processes these drugs.
Participant Groups
8Treatment groups
Experimental Treatment
Group I: Module 5 Part A : Dose escalation (AZD9574 + Dato-DXd)Experimental Treatment2 Interventions
Participants with advanced, unresectable, or metastatic solid tumours in different types of cancers will receive a combination of AZD9574 and Dato-DXd at escalating cohorts.
Group II: Module 4 Part A: Dose escalation (AZD9574 + T-DXdat)Experimental Treatment2 Interventions
Participants with advanced, unresectable, or metastatic solid tumours that are HER2-positive will receive a combination of AZD9574 and T-DXdat at escalating cohorts.
Group III: Module 3 Panel 3: AZD9574 monotherapy (Sweden only)Experimental Treatment1 Intervention
Participants with breast cancer (without BM).
Group IV: Module 3 Panel 2: AZD9574 + TMZ (Sweden only)Experimental Treatment1 Intervention
Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.
Group V: Module 3 Panel 1: AZD9574 monotherapy (Sweden only)Experimental Treatment1 Intervention
Participants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm.
Group VI: Module 2 Part A: Dose escalationExperimental Treatment2 Interventions
Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.
Group VII: Module 1 Part B: Dose expansionExperimental Treatment1 Intervention
Participants with breast cancer who are PARPi naive at doses determined in dose-escalation.
Group VIII: Module 1 Part A: Dose escalationExperimental Treatment1 Intervention
Participants with advanced/relapsed ovarian, breast, pancreatic, or prostate cancer who are deemed suitable for a PARPi will receive AZD9574 monotherapy at escalating cohorts.

Find a Clinic Near You

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a phase II trial involving 46 patients with progressive low-grade glioma, Temozolomide (Temodar) demonstrated a 61% objective response rate, with 24% achieving complete response and 37% achieving partial response.
The treatment showed promising safety, with limited toxicity observed; however, one patient experienced severe complications, highlighting the need for careful monitoring during treatment.
Phase II trial of temozolomide in patients with progressive low-grade glioma.Quinn, JA., Reardon, DA., Friedman, AH., et al.[2022]
Temozolomide (TMZ) has been established as an effective treatment for primary brain tumors like glioblastoma and oligodendroglioma, and it has also shown efficacy in melanoma, with multiple studies supporting its use as both a monotherapy and adjuvant chemotherapy.
Recent clinical trials suggest that TMZ may be beneficial in treating a variety of other cancers, including brain metastases, lymphomas, and neuroendocrine tumors, indicating its potential as a versatile cancer treatment beyond its formal indications.
Temozolomide and unusual indications: review of literature.Tatar, Z., Thivat, E., Planchat, E., et al.[2022]
Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.
Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.
Future directions for temozolomide therapy.Yung, WK.[2019]

References

Phase II trial of temozolomide in patients with progressive low-grade glioma. [2022]
Temozolomide and unusual indications: review of literature. [2022]
Future directions for temozolomide therapy. [2019]
Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. [2021]
Multicenter phase II trial of temozolomide in mycosis fungoides/sezary syndrome: correlation with O⁶-methylguanine-DNA methyltransferase and mismatch repair proteins. [2021]
Hematologic adverse events associated with temozolomide. [2018]
Role of temozolomide in pediatric brain tumors. [2022]
Temozolomide-induced myelodysplasia. [2020]
Temozolomide: a milestone in neuro-oncology and beyond? [2018]