Ceralasertib for Advanced Cancer

No longer recruiting at 22 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Strong CYP 3A inhibitors

Disqualifiers: Cardiac diseases, Active infections, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years 4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new treatment, Ceralasertib, against advanced cancers with certain genetic changes. The focus is on solid tumors with a specific alteration in the ATM gene, which can affect cancer growth and treatment response. There are two groups: one for advanced solid tumors (excluding lung cancer) and another for metastatic prostate cancer resistant to standard hormonal treatments. Participants must have a known diagnosis of one of these cancers and specific genetic changes in their tumor. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you do not use strong CYP 3A inhibitors and inducers while participating. If you are taking these, you may need to stop or switch medications.

Is there any evidence suggesting that Ceralasertib is likely to be safe for humans?

Research has shown that ceralasertib has been tested for safety in people with advanced solid tumors. In these studies, patients experienced some side effects, but they were usually manageable. Common issues included fatigue, nausea, and low blood counts. The medical team can help manage these side effects.

The treatment is currently in the middle stage of testing, indicating it has passed initial safety checks. This suggests it is considered reasonably safe for further study in more people. However, like any treatment, there are risks, so it is important to discuss these with the clinical trial team if considering participation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ceralasertib is unique because it targets cancers with ATM alterations through its inhibition of the ATR kinase, a key player in DNA damage response. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Ceralasertib offers a more tailored approach, potentially sparing healthy cells and reducing side effects. Researchers are excited about its promise in advanced cancers, particularly because it could offer new hope for patients with ATM-altered tumors who have limited options with current treatments.

What evidence suggests that Ceralasertib might be an effective treatment for advanced cancer?

Research has shown that ceralasertib, a drug affecting DNA repair in cells, has had limited success in treating certain advanced cancers with ATM changes. In studies, the drug reached the necessary blood levels but was not very effective at shrinking tumors. This trial will investigate ceralasertib as a monotherapy in two separate cohorts: Cohort A for participants with ATM-altered AST and Cohort B for participants with ATM-altered mCRPC. Scientists are examining how ceralasertib inhibits cancer cells from repairing their DNA, hoping this will lead to easier cancer cell death. Further research aims to understand its potential and improve its efficacy. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors containing specific ATM mutations, who have progressed on certain treatments like hormonal agents for prostate cancer. They must have normal organ and bone marrow function, no curative treatment options available, and can't join if they've had recent heart issues, uncontrolled medical conditions or infections.

Inclusion Criteria

Availability of archival or fresh tumour specimens for central testing of ATM protein loss using immunohistochemistry and for confirmation of ATM mutation using next generation sequencing.

Participants must have a deleterious or suspected deleterious ATM mutation in tumour or blood (germline or ctDNA). Definitions of qualifying ATM mutations may include deleterious/suspected deleterious, pathogenic/likely pathogenic, disease- or cancer-associated variants, or equivalent wording. Variants of unknown significance, benign or likely benign alterations are not qualifying.

Documented prostate cancer progression at study entry while on androgen deprivation or after bilateral orchiectomy as assessed by the investigator.

Exclusion Criteria

You have certain health conditions or a family history that could increase the risk of heart problems or abnormal heart rhythms.

Mean resting corrected QT interval (QTc) > 470 msec obtained from three electrocardiograms (ECGs) in 24 hours using the Fredericia formula.

Acute myocardial infarction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

2 visits (in-person)

Treatment

Participants receive oral dose of Ceralasertib 160 mg twice daily

Up to 2 years 4 months

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post last dose

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ceralasertib

Trial Overview The study tests the effectiveness of Ceralasertib in treating advanced cancers with ATM mutations. It looks at how safe it is and what side effects occur when used alone or combined with other drugs. Participants are selected based on their genetic profile related to these mutations.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 1 Intervention

Eligible participants (ATM altered mCRPC), will receive oral dose of Ceralasertib as monotherapy.

Group II: Cohort A Experimental Treatment 1 Intervention

Eligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy.

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

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT222/742542/Abstract-CT222-Efficacy-and-safety-of-ceralasertib

Abstract CT222: Efficacy and safety of ceralasertib in the ... Conclusion: Responses to ceralasertib monotherapy were limited in ATM-altered tumors, despite reaching target plasma levels. Alternative pt ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04564027

NCT04564027 | A Study Investigating DNA-damage ... Cohort A (Advanced Solid Tumours [AST]): A total of ~25 molecularly eligible and centrally confirmed participants dosed at ceralasertib 160 mg twice daily will ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D5339C00001

A Study Investigating DNA-damage Response Agents in ... Participants with ATM-altered aST received 160 mg of ceralasertib twice daily from Day 1 to Day 14 of 28 days cycle. Cohort B (mCRPC): 240 mg of Ceralasertib ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT04564027

A Study Investigating DNA-damage Response Agents ... A modular phase IIa multicenter open-label study evaluating the ATR inhibitor ceralasertib (AZD6738) in ATM mutant advanced solid tumors.

5. s3.amazonaws.com s3.amazonaws.com/ctr-med-7111/D5339C00001/c5913caa-a430-4d9b-a1d3-d55c7733c1c7/fc0baea3-ac1e-4856-9afb-446d2cc9fcf6/247947_CSR_synopsis_Final_Draft_to_approval__Redacted_16Apr24-v1.pdf

Title: A Modular Phase IIa Multicentre Open-Label Study to ... Conclusions for the primary analysis of efficacy of ceralasertib in patients in Cohort B with ATM-altered mCRPC, as assessed by composite ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04564027

NCT04564027 | A Study Investigating DNA-damage ... Eligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy. ... Eligible participants (ATM altered mCRPC), will receive oral ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03682289

NCT03682289 | Ceralasertib (AZD6738) Alone and in ... This phase II trial studies how well ceralasertib, am Ataxia telangiectasia and Rad3-related (ATR) kinase inhibitor, works alone or in combination with ...