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History of Changes for Study: NCT04564027
A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer
Latest version (submitted November 7, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 23, 2020 None (earliest Version on record)
2 December 8, 2020 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 February 18, 2021 Contacts/Locations and Study Status
4 March 19, 2021 Study Status and Contacts/Locations
5 April 16, 2021 Contacts/Locations and Study Status
6 May 21, 2021 Study Status and Contacts/Locations
7 June 18, 2021 Study Status
8 July 16, 2021 Study Status and Contacts/Locations
9 August 31, 2021 Outcome Measures, Study Description, Study Status and Eligibility
10 November 26, 2021 Study Status and Contacts/Locations
11 December 21, 2021 Contacts/Locations, Study Status and Study Design
12 January 20, 2022 Study Status
13 April 11, 2022 Study Status, Contacts/Locations and Study Design
14 May 11, 2022 Study Status
15 June 8, 2022 Study Status and Contacts/Locations
16 June 24, 2022 Eligibility, Study Description and Study Status
17 July 22, 2022 Study Status
18 September 5, 2022 Study Status
19 October 6, 2022 Study Status and Contacts/Locations
20 November 7, 2022 Study Status
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Study NCT04564027
Submitted Date:  September 23, 2020 (v1)

Open or close this module Study Identification
Unique Protocol ID: D5339C00001
Brief Title: A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer
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)
Secondary IDs:
Open or close this module Study Status
Record Verification: September 2020
Overall Status: Not yet recruiting
Study Start: October 23, 2020
Primary Completion: May 10, 2023 [Anticipated]
Study Completion: May 10, 2023 [Anticipated]
First Submitted: September 8, 2020
First Submitted that
Met QC Criteria:
September 23, 2020
First Posted: September 25, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
September 23, 2020
Last Update Posted: September 25, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: AstraZeneca
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: The study is investigating efficacy, safety and tolerability of DNA-damage Response Agents (or Combinations), in participants with advanced/metastatic solid malignancies whose tumours contain molecular alterations.
Detailed Description:

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 will be enrolled into this cohort (ensuring at least 60% of participants with ATM Immunohistochemistry [IHC] ≤ 5%).

Cohort B (Metastatic castration-resistant prostate cancer [mCRPC]): A total of ~27 molecularly eligible and centrally confirmed participants will be enrolled into Cohort B (ensuring at least 60% of participants with ATM IHC ≤ 5%). 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.

Open or close this module Conditions
Conditions: Advanced Solid Tumours
Keywords: Ataxia telangiectasia mutated
Metastatic castration-resistant prostate cancer
Rad3-related protein
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: N/A
Enrollment: 52 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cohort A
Eligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy.
Drug: Ceralasertib
Tablets will be administered orally
Other Names:
  • AZD6738
Experimental: Cohort B
Eligible participants (ATM altered mCRPC), will receive oral dose of Ceralasertib as monotherapy.
Drug: Ceralasertib
Tablets will be administered orally
Other Names:
  • AZD6738
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
2. 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.
Secondary Outcome Measures:
1. Cohort A: Duration of 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Cohort A and Cohort B: 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.
8. Cohort A and B: Number of participants with serious and non-serious adverse events
[ Time Frame: From screening (Day -28 to -1) until 30 days after last dose ]

To assess the safety and tolerability profile of ceralasertib.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 130 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Participants must have a histologically confirmed diagnosis of AST (excluding NSCLC) or mCRPC tumour.
  • Tumour must contain a deleterious ATM mutation, tested on a tumour specimen or circulating tumour deoxyribonucleic acid (DNA).
  • 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.

Exclusion Criteria:

  • Any of the following cardiac diseases currently or within the last 6 months:
    1. Unstable angina pectoris.
    2. Congestive heart failure > Class 2 as defined by the New York Heart Association
    3. Acute myocardial infarction.
    4. Significant ventricular or supraventricular arrhythmias.
    5. Mean resting corrected QT interval (QTc) > 470 msec obtained from three electrocardiograms (ECGs) in 24 hours using the Fredericia formula.
    6. 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.
    7. 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 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.
Open or close this module Contacts/Locations
Central Contact Person: AstraZeneca Clinical Study Information Center
Telephone: 1-877-240-9479
Email: information.center@astrazeneca.com
Locations:
Open or close this module IPDSharing
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:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Time Frame:
Access Criteria:
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Open or close this module References
Citations:
Links:
Available IPD/Information:

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