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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 : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumours Drug: Ceralasertib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : June 8, 2023
Estimated Study Completion Date : June 8, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort A
Eligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy.
Drug: Ceralasertib
Tablets will be administered orally
Other Name: 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 Name: AZD6738




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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

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


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, California
Research Site Recruiting
Duarte, California, United States, 91010
Research Site Not yet recruiting
La Jolla, California, United States, 92093
Research Site Not yet recruiting
San Francisco, California, United States, 94115
United States, Florida
Research Site Not yet recruiting
Tampa, Florida, United States, 33612
United States, Indiana
Research Site Recruiting
Indianapolis, Indiana, United States, 46202
United States, Maryland
Research Site Not yet recruiting
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Research Site Withdrawn
Boston, Massachusetts, United States, 02215
United States, Michigan
Research Site Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Nevada
Research Site Recruiting
Las Vegas, Nevada, United States, 89119
United States, New York
Research Site Not yet recruiting
New York, New York, United States, 10065
Research Site Not yet recruiting
Syracuse, New York, United States, 13210
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Research Site Recruiting
Myrtle Beach, South Carolina, United States, 29572
France
Research Site Not yet recruiting
Bordeaux, France, 33076
Research Site Not yet recruiting
Dijon, France, 21079
Research Site Not yet recruiting
Lyon, France, 69373
Research Site Not yet recruiting
Poitiers Cedex, France, 86021
Research Site Not yet recruiting
Vandoeuvre les Nancy, France, 54519
Spain
Research Site Not yet recruiting
Barcelona, Spain, 8035
Research Site Not yet recruiting
Cáceres, Spain, 10003
Research Site Not yet recruiting
Madrid, Spain, 28050
Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04564027    
Other Study ID Numbers: D5339C00001
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: April 19, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame:

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

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

Access Criteria:

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

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

URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Ataxia telangiectasia mutated
Metastatic castration-resistant prostate cancer
Rad3-related protein