Description:
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.
Title
- 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)
Clinical Trial IDs
- ORG STUDY ID:
D5339C00001
- NCT ID:
NCT04564027
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Ceralasertib | AZD6738 | Cohort A |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Cohort A | Experimental | Eligible participants (ATM altered AST), will receive oral dose of Ceralasertib as monotherapy. | |
| Cohort B | Experimental | Eligible participants (ATM altered mCRPC), will receive oral dose of Ceralasertib as monotherapy. | |
Eligibility 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.
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | Proportion of participants with a PSA decline of ≥ 50% confirmed by a second consecutive measurement at least 3 weeks later. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | rPFS is defined as the time from the start of treatment until the date of objective radiographic disease progression or death. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | Change in tumour size will be determined. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | To assess the safety and tolerability profile of ceralasertib. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AstraZeneca |
Trial Keywords
- Ataxia telangiectasia mutated
- Metastatic castration-resistant prostate cancer
- Rad3-related protein
Last Updated
July 19, 2021
