A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Nov 2021 → 18 Feb 2025

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB Forskargatan 18 Södertälje 151 85, Sweden

External identifiers

EU CT number

2024-515102-12-00

EudraCT number

2020-002529-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To obtain a preliminary assessment of the efficacy of study intervention as assessed by response rate.
Module 1 - Cohort A: To obtain a preliminary assessment of the efficacy of ceralasertib in participants with ATM altered aST refractory to standard treatments options, as assessed by ORR.
Module 1 - Cohort B: To obtain a preliminary assessment of the efficacy of ceralasertib in participants with ATM altered metastatic castration-resistant prostate cancer as assessed by composite response rate.

Secondary objectives 6

1. To obtain a preliminary assessment of further efficacy endpoints with study intervention.
2. To assess the safety and tolerability profile of study intervention.
3. Module 1 - Cohort A: To further assess the efficacy of ceralasertib.
4. Module 1 - Cohort A: To assess the safety and tolerability profile of ceralasertib.
5. Module 1 - Cohort B: To further assess the efficacy of ceralasertib.
6. Module 1 - Cohort B: To assess the safety and tolerability profile of ceralasertib.

Conditions and MedDRA coding

Advanced Cancer Whose Tumours Contain Molecular Alterations

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Capable of giving signed informed consent as described in Appendix B which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Provision of written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.
3. Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
4. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see Section 5.3.1).
5. Participant is willing and able to comply with the study protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
6. Participant must be able to swallow tablets whole.

Exclusion criteria 12

1. Persistent toxicities (> CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy.
2. History of another primary malignancy except for: - Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of study drug and of low potential risk for recurrence - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated carcinoma in situ without evidence of disease - Localised non-invasive primary under surveillance
3. Concurrent severe and/or uncontrolled medical condition (e.g., severe COPD, severe Parkinson’s disease, active inflammatory bowel disease) or psychiatric condition (screening for chronic disease is not required).
4. Participants with a known hypersensitivity to study interventions or any of the excipients of the products.
5. Major surgery within 2 weeks of starting study intervention: participants must have recovered from any effects of any major surgery.
6. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
7. Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
8. Previous enrolment in the present study.
9. Participants with gastrointestinal disorders likely to interfere with absorption of the study intervention.
10. Pregnant (confirmed with positive pregnancy test) or breast feeding women.
11. Previous allogenic bone marrow transplant.
12. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Module 1 - Cohort A: - Investigator assessed ORR, as defined by RECIST version 1.1.
2. Module 1 - Cohort B: -Composite response rate (investigator assessed radiological response as defined by RECIST 1.1 for soft tissue and visceral lesions and by PCWG3 for bone lesions, PSA decline, and/or CTC conversion).

Secondary endpoints 4

1. ​​For Core: ​- AEs/SAEs ​- Vital signs, ECG, clinical chemistry, haematology, urinalysis and coagulation parameters.
2. ​​Module 1 ​- AEs/SAEs ​- Vital signs, haematology and clinical chemistry parameters.
3. ​​Module 1 - Cohort A: ​-Investigator assessment, as defined by RECIST version 1.1: ​- DoR ​- Percentage change in tumour size ​- PFS​
4. ​​Module 1 - Cohort B: ​-ORR by RECIST 1.1 for soft tissue and visceral lesions and by PCWG3 ​criteria for bone lesions. ​-Proportion of participants with confirmed CTC count conversion from ​unfavourable to favourable. ​-Proportion of participants with confirmed PSA decline > 50%. ​-Best percentage change in tumour size. ​-Duration of radiological responses ​-Radiological PFS using RECIST 1.1 for soft tissues and visceral lesions ​and PCWG3 for bone lesions.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

​​AstraZeneca AB, Information Center​

Public contact point

Organisation

AstraZeneca AB

Contact name

​​AstraZeneca AB, Information Center​

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications