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
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Tablets will be administered orally
Research Site
Duarte, California, United States
Research Site
Los Angeles, California, United States
Research Site
Cohort A (aST): Objective Response Rate (ORR).
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. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.
Time frame: 2 years 4 months
Cohort B (mCRPC): Composite Response Rate.
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, confirmed prostate specific antigen (PSA) decline of more than 50%, and/or confirmed circulating tumour cell \[CTC\] conversion from unfavorable (\>=5 cells/7.5 ml blood) to favorable (\<5 cells). Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.
Time frame: Up to 2 years 4 months
Cohort A (aST): Duration of Radiological Response (DoR)
DoR is defined as the time from the date of first documented response (confirmed CR/PR) until date of documented progression or death in the absence of disease progression.
Time frame: Up to 2 years 4 months
Cohort A (aST): Progression Free Survival (PFS)
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San Francisco, California, United States
Research Site
Tampa, Florida, United States
Research Site
Indianapolis, Indiana, United States
Research Site
Baltimore, Maryland, United States
Research Site
Ann Arbor, Michigan, United States
Research Site
Las Vegas, Nevada, United States
Research Site
New York, New York, United States
Research Site
Ephrata, Pennsylvania, United States
...and 8 more locations
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. Progression is defined using (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.
Time frame: Up to 2 years 4 months
Cohort A (aST): Percentage Change in Tumor Size
Percentage change in tumour size is defined as the reduction from baseline or the 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. A negative change denotes a reduction in target lesion size.
Time frame: Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32), 5 (Week 40), 6 (Week (48), 7 (Week 56)
Cohort B (mRCPC): Percentage Change in Tumor Size
Percentage change in tumour size is defined as the reduction from baseline or the 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. A negative change denotes a reduction in target lesion size. Due to an increased frequency and early onset of Grade≥3 hematological toxicity noted among the participants receiving 240 mg of Ceralsertib, the sponsor decreased the dose to 160mg. Therefore, patients with the 240 mg BID starting dose were not included in the efficacy analyses for both study cohorts.
Time frame: Scan Visits 1 (Week 8), 2 (Week 16), 3 (Week 24), 4 (Week 32)
Cohort A (aST) and B (mCRPC): Number of Participants With Serious and Non-serious Adverse Events
The adverse events as a variable of safety and tolerability after admiration of ceralasertib was determined.
Time frame: From Screening (Day -28 to Day -1) Until Follow-up (30 days post last dose), up to 2 years 4 months