Studie för att utvärdera CCS1477 i avancerade tumörer
En öppen fas I/IIa-studie för att utvärdera säkerheten och effekten av CCS1477 som monoterapi och i kombination, hos patienter med avancerade solida/metastaserande tumörer.
A Phase 1/2a study to assess the safety, tolerability, PK and biological activity of CCS1477 in patients with metastatic castration resistant prostate cancer, metastatic breast cancer, non-small cell lung cancer or advanced solid tumours.
Studieöversikt
Status
Betingelser
Detaljerad beskrivning
The Steering Committee closed selected cohorts, in accordance with its responsibilities, after findings from earlier cohorts indicated that further evaluation of those cohorts was no longer warranted. The remaining cohorts were completed as specified in the protocol. Therefore, the study was considered completed.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
- Fas 1
Kontakter och platser
Studieorter
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Bordeaux, Frankrike, 33000
- Institute Bergonie
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Paris, Frankrike, 75015
- Hôpital Europeen Georges Pompidou
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Villejuif, Frankrike, 94805
- Institute Gustave Roussy
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Massachusetts
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Boston, Massachusetts, Förenta staterna, 02215
- Dana-Farber Cancer Institute
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Pennsylvania
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Philadelphia, Pennsylvania, Förenta staterna, 19107
- Thomas Jefferson University, Sidney Kimmel Cancer Center
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Amsterdam, Nederländerna, 1066 CX
- Netherlands Cancer Institute (NKI)
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Barcelona, Spanien, 08035
- Hospital Vall d'Hebron, VHIO
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Madrid, Spanien, 28050
- START CIOCC Hospital Universitario HM
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Belfast, Storbritannien, BT9 7AB
- Belfast City Hospital
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Birmingham, Storbritannien, B15 2TH
- Queen Elizabeth Hospital Cancer Centre
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Cambridge, Storbritannien, CB2 0QQ
- Cambridge University Hospital
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Edinburgh, Storbritannien, EH4 2XU
- Edinburgh Cancer Centre Western General Hospital
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Glasgow, Storbritannien, G12 0YN
- The Beatson West of Scotland Cancer Centre
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Leicester, Storbritannien, LE1 5WW
- Leicester Royal Infirmary
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Manchester, Storbritannien, M20 4BX
- The Christie Hospital
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Newcastle, Storbritannien, NE7 7DN
- Freeman Hospital
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Southampton, Storbritannien, SO16 6YD
- University Hospital Southampton
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Sutton, Storbritannien, SM2 5NG
- Royal Marsden Hospital
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Stockholm, Sverige, 171 76
- Karolinska Institute
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Provision of consent
- ECOG performance status 0-1
- Assessable disease (by CT, MRI, bone scan or X-ray)
- Adequate organ function
- Highly effective contraception measures for duration of study
Additional inclusion criteria for mCRPC patients only:
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Previously received abiraterone and/or enzalutamide (or equivalent anti-androgen), and docetaxel (unless ineligible or refused)
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Progressive disease documented by one or more of the following:
- Biochemical progression defined as at least 2 stepwise increases in a series of any 3 PSA values
- Progression as defined by RECIST v1.1 guideline for assessment of malignant soft tissue disease.
- Progression defined as two or more new metastatic bone lesions confirmed on bone scan from a previous assessment
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PSA at screening ≥2 μg/L
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Serum testosterone concentration ≤50 ng/dL
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Serum albumin >2.5 g/dL
Additional inclusion criteria for patients in CCS1477 plus abiraterone combination arm:
- Patients must have previously progressed on abiraterone treatment
- Patients whose last dose of abiraterone is greater than 6 months prior to start of study treatment will receive a 4-week run-in treatment with abiraterone to confirm refractoriness to abiraterone treatment
Additional inclusion criteria for patients in CCS1477 plus enzalutamide combination arm:
- Patients must have previously progressed on enzalutamide treatment
- Patients whose last dose of enzalutamide is greater than 6 months prior to start of study treatment will receive a 4-week run-in treatment with enzalutamide to confirm refractoriness to enzalutamide treatment
Additional inclusion criteria for patients in mutation arm:
- Advanced solid tumour with identification of markers which may indicate potential for response to p300/CBP inhibition. Markers include loss of function mutations in CREBBP, EP300 or ARID1A, MYC gene amplifications or rearrangements and androgen receptor (AR) gene amplifications or over-expression.
Exclusion Criteria:
- Intervention with any chemotherapy, investigational agents or other anti-cancer drugs within 14 days or 5 half-lives of the first dose
- Radiotherapy with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks of the first dose of study treatment
- Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study treatment
- Strong inhibitors of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment
- Strong inducers of CYP3A4 within 4 weeks of the first dose of study treatment
- Statins; patients should discontinue statins prior to starting study treatment
- Any unresolved reversible toxicities from prior therapy >CTCAE grade 1 at the time of starting study treatment
- Any evidence of severe or uncontrolled systemic diseases
- Any known uncontrolled inter-current illness
- QTcF prolongation (> 480 msec).
- Primary brain tumours or known or suspected brain metastases.
Additional exclusion criteria for patients in CCS1477 plus abiraterone combination arm:
- Clinically significant cardiac abnormalities
Additional exclusion criteria for patients in CCS1477 plus enzalutamide combination arm:
- History of seizures or other predisposing factors
- Use of substrates with a narrow therapeutic index metabolised by CYP2C9 or CYP2C19 within 2 weeks of the first dose of study treatment
- Clinically significant cardiac abnormalities
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Sekventiell tilldelning
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: CCS1477 dose escalation - mCRPC
CCS1477 monotherapy in patients with mCRPC |
Capsules, oral |
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Experimentell: CCS1477 expansion phase - mCRPC
CCS1477 monotherapy in patients with mCRPC |
Capsules, oral |
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Experimentell: CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC
CCS1477 plus abiraterone acetate in patients with mCRPC |
Capsules, oral Abiraterone acetate 500mg tablets plus prednisone/prednisolone |
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Experimentell: CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC
CCS1477 plus enzalutamide in patients with mCRPC |
Capsules, oral Enzalutamide 40mg capsules/tablets |
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Experimentell: CCS1477 Monotherapy - Solid tumours
CCS1477 expansion phase in patients with advanced solid tumours with molecular markers which may indicate potential for response to p300/CBP inhibition |
Capsules, oral |
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Experimentell: CCS1477 and darolutamide, combination dose finding and expansion - mCRPC
CCS1477 plus darolutamide in patients with mCRPC |
Capsules, oral 300mg tablets |
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Experimentell: CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer
CCS1477 plus olaparib in patients with mCRPC or metastatic breast cancer. |
Capsules, oral 150mg tablets |
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Experimentell: CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer
CCS1477 plus atezolizumab in patients with non-small cell lung cancer |
Capsules, oral 840mg/14ml concentrate for solution for infusion vials |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Withdrawal
Tidsram: From signing informed consent until the end of the follow-up period (Up to 363 weeks)
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Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study intervention, which does not necessarily have a causal relationship with the treatment. Serious AE (SAE) was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs were defined as those events with onset dates/time occurring after study intervention administration or events that worsen after study intervention administration. TEAEs included serious TEAEs and non-serious TEAEs. Number of participants with TEAEs leading to withdrawal of study intervention was also reported. |
From signing informed consent until the end of the follow-up period (Up to 363 weeks)
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Number of Participants With Worst Shift in Laboratory Data-Hematology According to Common Terminology Criteria for Adverse Events (CTCAE)-Version 5 Grades
Tidsram: From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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Adverse events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death related to the adverse event. Number of participants with worst shift in hematology according to Common Terminology Criteria for Adverse Events (CTCAE) grades were reported. |
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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Number of Participants With Worst Shift in Laboratory Data-Biochemistry According to Common Terminology Criteria for Adverse Events (CTCAE)-Version 5 Grades
Tidsram: From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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Adverse events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death related to the adverse event. Number of participants with worst shift in biochemistry according to Common Terminology Criteria for Adverse Events (CTCAE) grades were reported. |
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters - Urinalysis
Tidsram: From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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The urinalysis measurements included glucose, protein and blood. Number of participants with clinically significant changes from baseline in urinalysis values were reported. Clinically Significance was decided by investigator. |
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Tidsram: From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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The vital signs measurements included blood pressure, heart rate, respiration rate and temperature. Number of participants with clinically significant changes from baseline in vital signs values were reported. Clinically Significance was decided by investigator. |
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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Number of Participants With Worst Shift in QTcF According to Common Terminology Criteria for Adverse Events (CTCAE)-Version 5 Grades
Tidsram: From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
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Twelve-lead Electrocardiograms (ECGs) were obtained after the participant was in semi-supine for 5 minutes. Three ECGs were taken at each timepoint at about 1-minute intervals. QTcF was calculated using the Fridericia formula: QTcF = QT ÷ RR^(1/3), where QT is the measured QT interval in milliseconds and RR is the interval between two consecutive R waves on the ECG expressed in seconds. It was categorized as less than equal to (<=) 450 milliseconds (msec), more than (>) 450 to <=480 msec, > 480 to <= 500 msec and > 500 msec. |
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Best Percentage Change From Baseline in Prostate Specific Antigen (PSA) Response in Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC)
Tidsram: At Baseline - Cycle 1 - Day 1, Day 8, Day 15, Day 22 and Day 1 of every cycle from cycle 2 onwards until treatment discontinuation (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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Best percentage change from baseline was defined as the largest percentage reduction in PSA levels or the smallest percentage increase in PSA levels in the absence of a reduction. |
At Baseline - Cycle 1 - Day 1, Day 8, Day 15, Day 22 and Day 1 of every cycle from cycle 2 onwards until treatment discontinuation (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
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Number of Participants With CTC Response
Tidsram: From Baseline - Day 1 Cycle 1 (Predose), Day 1 Cycle 2, Day 1 Cycle 3, Day 1 Cycle 5 up to disease progression or treatment discontinuation (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
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CTC response was defined as a change from unfavourable (five or more cells per 7.5 mL of blood) at baseline to favourable (four or fewer cells per 7.5 mL) post treatment. Number of participants with overall response were reported. A participant was determined as having an overall CTC response if they had at least one post baseline assessment of 'CTC response'. |
From Baseline - Day 1 Cycle 1 (Predose), Day 1 Cycle 2, Day 1 Cycle 3, Day 1 Cycle 5 up to disease progression or treatment discontinuation (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
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Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Tidsram: From day of study intervention in Cycle 1 until progression or censoring date in the absence of progression (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
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Objective response is defined as any participant with measurable disease who has a best overall response of Partial Response (PR) or Complete Response (CR). CR is defined as the disappearance of all Target Lesions (TLs) since baseline. PR is defined as At least a 30% decrease in the sum of diameters of TLs, taking as reference the baseline sum of diameters. |
From day of study intervention in Cycle 1 until progression or censoring date in the absence of progression (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
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Radiological Progression Free Survival (rPFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Tidsram: From day of study intervention in Cycle 1 until progression or censoring date in the absence of progression (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
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Radiological progression free survival (rPFS) was defined as the time from the start of treatment with CCS1477 in Cycle 1 until the earliest objective disease progression defined by RECIST 1.1, Prostate Cancer Clinical Trial Working Group 3 (PCWG-3) bone progression or death by any cause in the absence of progression, regardless of whether the participants withdraws from study medication or receives another anti-cancer therapy prior to progression. Kaplan - Meier estimate was used to calculate the rPFS. |
From day of study intervention in Cycle 1 until progression or censoring date in the absence of progression (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
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Overall Survival (OS)
Tidsram: From start of treatment until death (Up to 363 weeks)
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Overall survival is defined as the time from the start of treatment with CCS1477 in Cycle 1 until death due to any cause. |
From start of treatment until death (Up to 363 weeks)
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Maximum Observed Plasma Concentration (Cmax)
Tidsram: Cycle 1 Day 1 and Cycle 2 Day 3 (Cycle length was 4 weeks)
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Cmax was obtained directly from concentration versus time curve. |
Cycle 1 Day 1 and Cycle 2 Day 3 (Cycle length was 4 weeks)
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Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-24)
Tidsram: Cycle 1 Day 1 and Cycle 2 Day 3 (Cycle length was 4 weeks)
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AUC0-24 is defined as the area under the concentration-time curve (AUC) from time zero (= dosing time) to 24 hours. AUC0-24 was calculated using the mixed log-linear trapezoidal rule. |
Cycle 1 Day 1 and Cycle 2 Day 3 (Cycle length was 4 weeks)
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Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Johann de Bono, MD, Royal Marsden NHS Foundation Trust
Publikationer och användbara länkar
Allmänna publikationer
- Eickhoff N, Bergman AM, Zwart W. Homing in on a Moving Target: Androgen Receptor Cistromic Plasticity in Prostate Cancer. Endocrinology. 2022 Oct 11;163(11):bqac153. doi: 10.1210/endocr/bqac153.
- Caligiuri M, Williams GL, Castro J, Battalagine L, Wilker E, Yao L, Schiller S, Toms A, Li P, Pardo E, Graves B, Azofeifa J, Chicas A, Herbertz T, Lai M, Basken J, Wood KW, Xu Q, Guichard SM. FT-6876, a Potent and Selective Inhibitor of CBP/p300, is Active in Preclinical Models of Androgen Receptor-Positive Breast Cancer. Target Oncol. 2023 Mar;18(2):269-285. doi: 10.1007/s11523-023-00949-7. Epub 2023 Feb 24.
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Neoplasmer efter plats
- Neoplasmer
- Luftvägssjukdomar
- Lungsjukdomar
- Neoplasmer i andningsvägarna
- Thoracic neoplasmer
- Lungneoplasmer
- Hudsjukdomar
- Bröstsjukdomar
- Karcinom, bronkogent
- Bronkiella neoplasmer
- Hud- och bindvävssjukdomar
- Bröstneoplasmer
- Karcinom, icke-småcellig lunga
- Polycykliska föreningar
- Steroider
- Fusion-ringföreningar
- Androstenes
- Androstaner
- Abirateronacetat
- darcutamid
- enzalutamid
- atezolizumab
- olaparib
- CCS1477
Andra studie-ID-nummer
- CCS1477-01
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
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