Module 1A: All solid malignancies Module 1B: Solid malignancies, potentially including TNBC, SCLC, CRPC, ovarian cancer patients, and other appropriate cancer indications. Module 1B-1 (TNBC): Metastatic or recurrent TNBC Module 2: Metastatic or locally advanced HR+ and HER2- breast cancer in patients who had previously received an aromatase inhibitor and a CDK4/6 inhibitor Module 4: All solid malignancies
Conditions
Interventions
Product Name: CDK7 Inhibitor
Product Code: CT7001
Pharmaceutical Form: Capsule
INN or Proposed INN: CT7001
Other descriptive name: CT7001
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Carrick Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Core Inclusion Criteria: 1. At least 18 years of age 2. ECOG performance status 0 or 1 with no deterioration over the previous 2 weeks 3. Estimated life expectancy of greater than 12 weeks 4. Ability to swallow and retain oral medication 5. Women of childbearing potential must be willing to practice effective contraception (per protocol definition) for the duration of the study and for 6 months after the last dose of CT7001 6. Criteria to identify women not of childbearing potential are defined in the protocol 7. Sexually active male subjects must be willing to use contraception per protocol description 8. Provision of signed and dated, written informed consent before any study-specific procedures, sampling, or analyses, including access to archival tumour tissue. Host Genetics Research Study: Pharmacogenetics Samples (Optional): 1. Provision of signed and dated, written informed consent for the genetic research. Module 1A Breast Cancer Cohort additional Inclusion Criteria: 1. Histological, radiological or cytological confirmation of breast cancer not considered to be appropriate for further standard treatment. Module 1A Breast Cancer or Solid Tumour Cohort additional Inclusion Criteria: 1. At least one tumour suitable for repeat biopsy from the same lesion. Module 1B additional Inclusion Criteria: 1. Histological, radiological or cytological confirmation of metastasis or locally advanced tumour not considered to be appropriate for further standard treatment 2. At least one line of systemic anti-cancer therapy. 3. Disease must be measurable by Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1), per protocol description. Module 1B-1 (TNBC) additional Inclusion Criteria: 1. Histologically confirmed carcinoma of the breast not expressing oestrogen receptor (ER) and progesterone receptor (PgR) and negative for human epidermal growth factor receptor 2 (HER2), per protocol description 2. Metastatic or locally advanced disease not amenable to resection or radiation therapy with curative intent with documented progressive disease on or within 6 months of most recent prior chemotherapy. 3. Disease must be measurable by Response Evaluation Criteria in Solid Tumors (RECIST, version 1. 1), per protocol description Module 2 will have standalone eligibility criteria with the principal inclusion defined as below: 1. Women 18 years of age or older who are either: o post-menopausal or pre/peri-menopausal. as defined by one of the following criteria: OR o Pre/peri-menopausal, i.e., not meeting the criteria for being postmenopausal, if amenable to treatment with the LHRH agonist goserelin. 5. Histologically confirmed diagnosis of carcinoma of the breast with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent. 6. Documentation of ER-positive and/or PgR-positive tumour based on most recent tumour biopsy utilizing an assay consistent with local standards. 7. Documentation of HER2 negativity based on local testing on most recent tumour biopsy. 8. Measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. 9. Patients must have documented objective disease progression while on or within 6 months after the end of the most recent therapy. 10. Patients must have received an aromatase inhibitor together with a CDK4/6 inhibitor in the same line of therapy for the treatment of: o locally
Exclusion criteria
Exclusion criteria: Core Exclusion Criteria: 1. Any other malignancy which has been active or treated within the past 3 years, with the exception per protocol description. 2. Any unresolved toxicity (except alopecia) from prior therapy of = Grade 2 according to the Common Terminology Criteria for Adverse Events (CTCAE). 3. Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroids for at least 4 weeks before the first dose of IP. 4. Refractory nausea and vomiting, chronic GI diseases or previous significant bowel resection, with clinically significant sequelae that would preclude adequate absorption of CT7001. 5. Uncontrolled seizures. 6. Active infection requiring systemic antibiotic, antifungal, or antiviral medication 7. Severe or uncontrolled medical condition or psychiatric condition 8. Active bleeding diatheses 9. Renal transplant 10. Known hepatitis B, hepatitis C, or human immunodeficiency virus infection 11. Breastfeeding or pregnancy 12. Receipt of cytotoxic treatment for the malignancy per protocol description 13. Receipt of noncytotoxic treatment for the malignancy within 5 half-lives of the drug before the first dose of IP 14. Receipt of corticosteroids per protocol description 15. Receipt of any small-molecule investigational medicinal product (IMP) per protocol description 16. Receipt of any biological or non-biological anti-cancer medicine per protocol description 17. Receipt of St John’s Wort within 21 days before the first dose of IP or of another concomitant medication, herbal supplement, or food that is a strong inhibitor or inducer of CYP3A4, CYP2C19, CYP2D6, or P-glycoprotein activity per protocol description 18. Receipt of a blood transfusion (blood or blood products) per protocol description 19. Known hypersensitivity to CT7001 or any excipient of the product 20. Impaired hepatic or renal function 21. Liver function deteriorating in a manner per protocol description 22. Other evidence of impaired hepatic synthesis function 23. Inadequate bone marrow reserve or organ function 24. Persistent severe pancytopenia due to previous therapy rather than to disease 25. Cardiac dysfunction 26. Mean resting QT interval corrected for heart rate by the Fridericia formula (QTcF) > 470 msec 27. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG. Controlled atrial fibrillation (AF) is permitted 28. Any factor that increases the risk of QTc prolongation or of arrhythmic events (e.g. per protocol description) 29. In the opinion of the Investigator, unlikely to comply with study procedures, restrictions, or requirements 30. A history of haemolytic anaemia or marrow aplasia 31. Has received a live-virus vaccination within 28 days or less of planned treatment start. Host Genetics Research Study: Pharmacogenetics Samples (Optional), Exclusion Criteria 1. Allogenic bone marrow transplant. 2. Non-leucocyte-depleted whole blood transfusion within 120 days of the date of the genetic sample collection. Additional Exclusion Criteria (Module 1 Part A) International normalised ratio (INR) = 1.5. Module 1B: No additional exclusion criteria to core. Module 1B-1 (TNBC) additional Exclusion Criteria: 1. More than three lines of chemotherapy for metastatic and/or locally advanced disease. 2. Advanced, symptomatic, visceral metastases if risk of life-threatening complications in the short term Module 2 1. Prior therapy with fu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Module 1A: To select the CT7001 dose(s) and schedule(s) for further clinical evaluation in patients with advanced solid malignancies. Module 1B: To assess the biological and anti-tumour activity of CT7001, given as a monotherapy. Module 1B-1 (TNBC): To further characterize the safety and tolerability of CT7001 and determine the most appropriate dosing regimen for subsequent Phase 2 testing (definitive RP2D). Module 2A: To determine the recommended Phase 2 dose of CT7001 given in combination with fulvestrant at 500 mg Module 2B: To compare the efficacy of CT7001 given in combination with fulvestrant versus fulvestrant plus placebo. Module 2C: To evaluate the efficacy of CT7001 combined with fulvestrant in patients whose disease had progressed on or after fulvestrant plus placebo in Part B of the study. Module 4: To evaluate the effect of food on the total and peak exposure of CT7001 when dosed as a capsule formulation to patients with advanced solid malignancies.;Secondary Objective: M1A: Characterise CT7001 PK after single dose and at steady state after multiple dosing Assess biological and anti tumour activity of CT7001 M1B and M1B-1 (TNBC): Eval. the activity of CT7001 as monotherapy. Further eval. CT7001 plasma concentrations. Eval. CYP2D6 polymorphisms in this patient population. M2: Eval. safety and tolerability Eval. CT7001 trough concentrations in combination with fulvestrant compared to historical CT7001 data Eval. correlations between CT7001 exposures and efficacy/safety findings in patient population Eval. incidence, genotypes and copy number variation of CYP and drug transporter genes that may be involved in CT7001 metabolism M2B only: Compare Patient Reported Outcomes between treatment arms Eval. fulvestrant plasma concentrations in combination with CT7001 or placebo M4: No additional objectives;Primary end point(s): Module 1A: • AEs • Clinical laboratory results (haematology, serum chemistry, coagulation, urinalysis) • Phys | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Module 1A: • PK Parameters for CT7001 • Biological Activity Parameters (Biomarkers) • Anti-tumour Activity Module 1B and 1B-1 (TNBC): • Objective response rate (ORR) • Duration of response (DOR) • Disease control (DC: CR or PR or SD =24 weeks) • Best percent tumour size change • Progression-free survival (PFS) • Trough plasma concentrations of CT7001 Module 4: No additional secondary endpoints to core protocol. Module 2 all study parts: • Duration of response (DOR) • Clinical Benefit Response (CBR) (complete or partial response, or stable disease =24 weeks • Trough plasma concentrations of CT7001 • Incidence and type of genotypes and copy number variation of CYP2D6, other CYP genes and drug transporter genes that may be involved in the metabolism of CT7001 Module 2A and 2B only: • Objective response rate (ORR) • Trough plasma concentrations of fulvestrant Module 2A and 2C only: • Best percent change in tumour size Module 2B only: • Patient Reported Outcome endpoints such as health related quality of life scores: o EuroQol (EQ-5D) Score; European Organisation for Research and Treatment of Cancer Quality of Life Instrument (EORTC QLQ-C30); European Organisation for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ-BR23]).;Timepoint(s) of evaluation of this end point: Module 1A Efficacy (anti-tumour activity): Every 6 weeks on therapy, every 3 months during follow up. Biomarkers assessed at screening, cycle 0, cycle 1, and Day 1 of each subsequent cycle, and at End of Treatment. PK assessed at cycle 0, 1, 2, 3 and every other cycle onwards, and at End of Treatment. Module 1B 1B-1 Efficacy (ORR, DOR, DC, best % tumour size change, PFS): Every 8 weeks on therapy, every 3 months during follow up. PK assessed at all cycles, and at End of Treatment. Module 2 Efficacy (ORR, DOR, CBR, best percent tumour size change): every 8 weeks on therapy, every 12 weeks during follow up. PK assessed at | — |
Countries
Spain, United Kingdom, United States
Contacts
Public ContactProject Manager
Emas Pharma Ltd T/A Bionical
Outcome results
None listed