Clinical trial NCT04564027: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Solid Tumours
Keywords: Ataxia telangiectasia mutated
Metastatic castration-resistant prostate cancer
Rad3-related protein
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.

Eligibility criteria: Inclusion Criteria:

* 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.

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 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.

Primary outcomes:
measure: Cohort A (aST): Objective Response Rate (ORR).
timeFrame: 2 years 4 months
measure: Cohort B (mCRPC): Composite Response Rate.
timeFrame: Up to 2 years 4 months
Secondary outcomes:
measure: Cohort A (aST): Duration of Radiological Response (DoR)
timeFrame: Up to 2 years 4 months
measure: Cohort A (aST): Progression Free Survival (PFS)
timeFrame: Up to 2 years 4 months
measure: Cohort A (aST): Percentage Change in Tumor Size
timeFrame: Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32), 5 (Week 40), 6 (Week (48), 7 (Week 56)
measure: Cohort B (mRCPC): Percentage Change in Tumor Size
timeFrame: Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32)
measure: Cohort A (aST) and B (mCRPC): Number of Participants With Serious and Non-serious Adverse Events
timeFrame: From Screening (Day -28 to Day -1) Until Follow-up (30 days post last dose), up to 2 years 4 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: New York
country: United States
facility: Research Site
state: New York
city: Ephrata
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Research Site
state: South Carolina
city: Bordeaux
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
Study officials:
References: