A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer
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|ClinicalTrials.gov Identifier: NCT04564027|
Recruitment Status : Recruiting
First Posted : September 25, 2020
Last Update Posted : February 21, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumours||Drug: Ceralasertib||Phase 2|
Current module of the study will consist of 2 cohorts as follows:
Cohort A (Advanced Solid Tumours [AST]): A total of ~25 molecularly eligible and centrally confirmed participants dosed at ceralasertib 160 mg twice daily will be enrolled into this cohort.
Cohort B (Metastatic castration-resistant prostate cancer [mCRPC]): A total of ~27 molecularly eligible and centrally confirmed participants dosed at ceralasertib 160 mg twice daily will be enrolled into Cohort B. Unfavourable circulating tumour cells (CTC) count requirement may be introduced for all participants to ensure an adequate (approximately ≥ 50%) number of participants with CTC count ≥ 5/7.5 mL blood.
The screening will have 2 parts, Part 1 and Part 2, which apply for both Cohort A and Cohort B.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||61 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Modular Phase 2a Multicentre Open-Label Study to Investigate DNA-damage Response Agents (or Combinations) in Patients With Advanced Cancer Whose Tumours Contain Molecular Alterations (PLANETTE)|
|Actual Study Start Date :||December 1, 2020|
|Estimated Primary Completion Date :||October 16, 2023|
|Estimated Study Completion Date :||October 16, 2023|
Experimental: Cohort A
Eligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy.
Tablets will be administered orally
Other Name: AZD6738
Experimental: Cohort B
Eligible participants (ATM altered mCRPC), will receive oral dose of Ceralasertib as monotherapy.
Tablets will be administered orally
Other Name: AZD6738
- Cohort A: Objective response rate (ORR) by response evaluation ceiteria in solid tumours (RECIST) version 1.1 [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]ORR is defined as the percentage of participants who have at least one response of complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by response evaluation criteria in solid tumours [RECIST] 1.1) that is confirmed at least 4 weeks later.
- Cohort B: Composite response rate by RECIST version 1.1 [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]Composite response rate is defined as the investigator assessed radiological response by RECIST 1.1 for soft tissue and visceral lesions and prostate cancer working group 3 (PCWG3) for bone lesions, prostate specific antigen (PSA) decline, and/or circulating tumour cell [CTC] conversion.
- Cohort A: Duration of Radiological response (DoR) by RECIST version 1.1 [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]DoR is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
- Cohort A: Progression free survival (PFS) by RECIST version 1.1 [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]PFS is defined as the time from start of study intervention until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy prior to progression.
- Cohort B: ORR by RECIST version 1.1 [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]Radiological ORR is defined as the percentage of participants with a confirmed response of CR or PR in their soft tissue and visceral lesions assessed by RECIST 1.1 in the absence of bone progression assessed by PCWG3.
- Cohort B: Proportion of participants with confirmed CTC count conversion from unfavourable to favourable [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]Conversion of CTC count is defined as a conversion from unfavourable at baseline (≥ 5/7.5 mL blood) to favourable post-baseline (< 5/7.5 mL blood). The percentage of participants with CTC count conversion based on those with unfavourable CTC at baseline, will be presented for this study.
- Cohort B: Proportion of participants with confirmed prostate specific antigen (PSA) decline ≥ 50% [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]Proportion of participants with a PSA decline of ≥ 50% confirmed by a second consecutive measurement at least 3 weeks later.
- Cohort B: Radiological progression free survival (rPFS) by RECIST 1.1 [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]rPFS is defined as the time from the start of treatment until the date of objective radiographic disease progression or death.
- Cohort B: Duration of radiological response. [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]DoR is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
- Cohort A and Cohort B: Best percentage change in tumour size [ Time Frame: From Screening (Day -28 to -1) until disease progression or withdrawal of consent (upto approximately 3 years) ]Change in tumour size will be determined. Best percentage change in tumour size is defined as the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction in the sum of the longest diameters (or the short axis measurements for lymph nodes) of the target lesions.
- Cohort A and B: Number of participants with serious and non-serious adverse events [ Time Frame: From Screening (Day -28 to Day -1) until Safety follow-up (30 days after last dose) (upto approximately 3 years) ]To assess the safety and tolerability profile of ceralasertib.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 130 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Participants must have a histologically confirmed diagnosis of AST (excluding NSCLC) or mCRPC tumour.
- 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.
- Participant must have normal organ and bone marrow function measured within 28 days prior to the first dose of study intervention.
- Participants who have no curative treatment options and are deemed appropriate for an investigational study in the opinion of the investigator.
- 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.
- Previously received and progressed on at least one novel hormonal agent (eg, abiraterone acetate, apalutamide, and/or enzalutamide) for the treatment of prostate cancer
- Participants with histologically confirmed metastatic castrate resistant prostate cancer.
- Documented prostate cancer progression at study entry while on androgen deprivation or after bilateral orchiectomy as assessed by the investigator.
- Serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within (≤) 28 days before enrolment.
Any of the following cardiac diseases currently or within the last 6 months:
- Unstable angina pectoris.
- Congestive heart failure > Class 2 as defined by the New York Heart Association
- Acute myocardial infarction.
- Significant ventricular or supraventricular arrhythmias.
- Mean resting corrected QT interval (QTc) > 470 msec obtained from three electrocardiograms (ECGs) in 24 hours using the Fredericia formula.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age.
- For Cohort B (mCRPC]), surgery or local prostatic intervention (excluding a prostatic biopsy) within 28 days of Cycle 1 Day 1.
- Participants with known active infections ((i.e., hepatitis B or C, tuberculosis, or COVID-19).
- Participants considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
- Participants with symptomatic and/or uncontrolled brain metastases.
- Previous therapy with an telangiectasia and rad3 related protein inhibitor.
- Exposure to a small molecule investigational product within 14 days or 5 half-lives.
- Concomitant use of known strong CYP 3A inhibitors and inducers.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04564027
|Contact: AstraZeneca Clinical Study Information Centeremail@example.com|
|United States, Arizona|
|Tucson, Arizona, United States, 85719|
|United States, California|
|Beverly Hills, California, United States, 90211|
|Duarte, California, United States, 91010|
|La Jolla, California, United States, 92093|
|Los Angeles, California, United States, 90089|
|Sacramento, California, United States, 95817|
|San Francisco, California, United States, 94115|
|United States, Florida|
|Tampa, Florida, United States, 33612|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|United States, Louisiana|
|New Orleans, Louisiana, United States, 70056|
|United States, Maryland|
|Baltimore, Maryland, United States, 21231|
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02215|
|United States, Michigan|
|Ann Arbor, Michigan, United States, 48109|
|United States, Minnesota|
|Saint Paul, Minnesota, United States, 55102|
|United States, Nevada|
|Las Vegas, Nevada, United States, 89119|
|United States, New York|
|New York, New York, United States, 10065|
|Syracuse, New York, United States, 13210|
|United States, Pennsylvania|
|Ephrata, Pennsylvania, United States, 17522|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, South Carolina|
|Myrtle Beach, South Carolina, United States, 29572|
|Bordeaux, France, 33076|
|Dijon, France, 21079|
|Lyon, France, 69373|
|Poitiers Cedex, France, 86021|
|Vandoeuvre les Nancy, France, 54519|
|Barcelona, Spain, 08036|
|Barcelona, Spain, 08907|
|Barcelona, Spain, 8035|
|Cáceres, Spain, 10003|
|Madrid, Spain, 28034|
|Madrid, Spain, 28041|
|Madrid, Spain, 28050|
|Other Study ID Numbers:||
|First Posted:||September 25, 2020 Key Record Dates|
|Last Update Posted:||February 21, 2023|
|Last Verified:||February 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the requests portal. All request will be evaluated as per the AZ disclosure commitment:
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Statistical Analysis Plan (SAP)
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Ataxia telangiectasia mutated
Metastatic castration-resistant prostate cancer