Modular Study to Evaluate CT7001 Alone in Cancer Patients With Advanced Malignancies

NCT ID: NCT03363893

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-14
• Study Completion Date: 2022-12-15

Brief Summary

This is a modular, Phase I/II, multicentre study to investigate CT7001 monotherapy in advanced solid malignancies and to further investigate CT7001 as monotherapy or in combination with standard therapy in specific participant groups with Triple Negative Breast Cancer (TNBC), Castrate Resistant Prostate Cancer (CRPC) and in combination with fulvestrant for patients with hormone receptor-positive (HR+ve) / human epidermal growth factor-2 negative (HER2-ve) breast cancer.

Detailed Description

Module 1 comprises two sequential parts:

• Part A: First-in-human (FiH) dose escalation investigating the safety and tolerability of CT7001 to identify the minimum biologically active dose (MBAD) and maximum tolerated dose (MTD). Part A also includes a cohort expansion for breast cancer participants only: this includes sequential tumour biopsies for evaluation of pharmacokinetic (PK), pharmacodynamic (PD) and tumour responses. The module is completed.
• Part B: To refine the safety, tolerability, and PK and PD profiles of CT7001 monotherapy in participants with advanced solid malignancies from up to four tumour- specific cohorts, which may include, but is not limited to, triple-negative breast cancer, ovarian cancer, small-cell lung cancer and prostate cancer.

• Part B, Cohort 1, Triple-Negative Breast Cancer (M1B-1 TNBC) treated with CT7001 as monotherapy. The module is completed.
• Part B, Cohort 2, Prostate Cancer (M1B-2 CRPC) treated with CT7001 as monotherapy. The module is completed.
• Module 2 is a Phase Ib/II, 3-part safety and efficacy study in participants with hormone- receptor positive (HR+ve) and human epidermal growth factor-2 negative (HER2-ve) breast cancer. This module includes dosing CT7001 in combination with fulvestrant. Module 2 was planned to comprise of 3 parts; Part A (open-label, single-arm, ascending dose study), Part B (double blinded, randomised, placebo-controlled study) and Part C (crossover from Part B). However, only Module 2 Part A was initiated and completed. Therefore, further sections of this record only reflect Module 2 Part A information.
• Module 4 is a study investigating the effect of food on the PK of CT7001 monotherapy in participants with advanced solid malignancies. The module is completed.
• Module 6 was planned as a Phase 1 study to explore the tolerability of, and the total and peak exposure of, an enteric capsule formulation of CT7001 [CT7001(EC)], when given as monotherapy to patients with advanced solid malignancies. Module 6 was not initiated.

Conditions

Advanced Solid Malignancies

Keywords

Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Module 1 Part A Multiple ascending dose cohort and Paired Biopsy Breast Cancer Expansion Cohort

Module 1 Part A Multiple ascending dose cohort: Participants with advanced solid tumours receive CT7001 (samuraciclib) as oral monotherapy, in ascending dose cohorts, to identify the maximum tolerated dose (MTD), minimally biologically active dose (MBAD) and recommended dose for Phase II testing (RP2D).

Following completion of the dose escalation part of Module 1A, participants to receive safe, tolerable and MBAD of CT7001 for the paired biopsy expansion cohort.

Module 1 Part A Paired Biopsy Breast Cancer Expansion Cohort: Participants with locally advanced or metastatic breast cancer will receive CT7001 (samuraciclib) as oral monotherapy at the minimally biologically active dose (MBAD) and recommended dose for Phase II testing (RP2D).

Group Type: EXPERIMENTAL

CT7001

Intervention Type: DRUG

Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression

Module 1 Part B-1 Triple-negative breast cancer (TNBC) Expansion

Participants with locally advanced or metastatic triple-negative breast cancer (TNBC) will receive CT7001(samuraciclib) as oral monotherapy at the dose, frequency and schedule recommended from Module 1 Part A.

Group Type: EXPERIMENTAL

CT7001

Intervention Type: DRUG

Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression

Module 1 Part B-2 Castrate resistant prostate Cancer (CRPC) Expansion

Participants with castrate resistant prostate cancer will receive CT7001(samuraciclib) as oral monotherapy at the dose, frequency and schedule recommended from Module 1 Part A.

Group Type: EXPERIMENTAL

CT7001

Intervention Type: DRUG

Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression

Module 2 Part A

Participants with locally advanced or metastatic HR+ve and HER2-ve breast cancer will receive CT7001 (samuraciclib) at the dose, frequency and schedule recommended from Module 1 part A and will receive Fulvestrant solution in pre-filled syringe for intramuscular (IM) injection

Group Type: EXPERIMENTAL

CT7001

Intervention Type: DRUG

Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression

Fulvestrant

Intervention Type: DRUG

Administered as 2 x 250mg intramuscular (IM) gluteal injections on Day 1, Day 15, Day 28 and every 28 days thereafter.

Module 4

Participants with advanced solid tumours will receive CT7001(samuraciclib) oral monotherapy in a randomized, balanced, single-dose, two-treatment (fed v fasting), two-period, two-sequence crossover study followed by once daily continuous dosing.

Group Type: EXPERIMENTAL

CT7001

Intervention Type: DRUG

Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression

Interventions

CT7001

Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression

Intervention Type: DRUG

Fulvestrant

Administered as 2 x 250mg intramuscular (IM) gluteal injections on Day 1, Day 15, Day 28 and every 28 days thereafter.

Intervention Type: DRUG

Other Intervention Names

Samuraciclib; Faslodex

Eligibility Criteria

Inclusion Criteria

1. ECOG performance status 0 or 1 with no deterioration over the previous 2 weeks

2. Estimated life expectancy of greater than 12 weeks

3. Ability to swallow and retain oral medication

4. Women either of non-childbearing potential or of childbearing potential willing to practice effective contraception for the duration of the study and for 6 months (Module 1, Module 4) and 24 months (Module 2) after the last dose of CT7001

5. Sexually active male patients must be willing to use condoms with all sexual partners for the duration of the study and for 3 months after the last dose of CT7001.

6. Provision of signed and dated, written informed consent

1. Histological, radiological or cytological confirmation of an advanced non-haematological malignancy not considered to be appropriate for further standard treatment

2. Module 1A biopsy cohort only : at least one tumour suitable for repeat biopsy

1. Histological or cytological confirmation of metastasis or locally advanced tumour

2. At least one line of systemic anti-cancer therapy

3. Disease measurable by RECIST v1.1

1. Histologically-confirmed carcinoma of breast not expressing oestrogen receptor (ER) or progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2)

2. Documented disease progression on or within 6 months of most recent cytotoxic prior cytotoxic chemotherapy

3. Disease measurable by RECIST v1.1

4. Must have received at least one cytotoxic chemotherapy for metastatic/locally advanced disease

1. Women only

2. Pre- or peri-menopausal women must have initiated LHRHa at least 28 days prior to first dose of CT7001/placebo

3. Histologically-confirmed, metastatic or locally advanced, ER+ve and/or PGR+ve and HER2-ve breast cancer

4. Disease measurable by RECIST v1.1

5. Documented objective disease progression while on, or within 6 months after the end of, the most recent therapy

6. Must have received an aromatase inhibitor together with a CDK4/6 inhibitor in the same line of therapy for locally advanced or metastatic disease or for treatment of early breast cancer if the disease-free interval was <12 months.

7. Ability to receive intramuscular injections.

1. Patients must be able to eat a high-fat meal, as provided by the study site, within a 30-minute period

2. Histological, radiological or cytological confirmation of an advanced non-haematological malignancy not considered to be appropriate for further standard treatment

Exclusion Criteria

1. Any other malignancy that has been active or treated within the past 3 years, with the exception of cervical intraepithelial neoplasia and non-melanoma skin cancer

2. Any unresolved toxicity (except alopecia) from prior therapy of ≥ CTCAE Grade 2

3. Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroids for at least 4 weeks before the first dose of investigational product (IP)

4. Refractory nausea and vomiting, chronic gastrointestinal (GI) disease 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 systemic cytotoxic treatment for the malignancy within 28 days or ≤ 5 half-lives, whichever is shorter before the first dose of IP

13. Receipt of non-cytotoxic treatment for the malignancy within 5 half-lives of the drug before the first dose of IP

14. Receipt of corticosteroids (at a dose > 10 mg prednisone/day or equivalent) within 14 days before the first dose of IP

15. Receipt of any small-molecule investigational medicinal product (IMP) within 28 days or ≤ 5 half-lives, whichever is shorter before the first dose of IP

16. Receipt of any biological IMP (e.g., immune checkpoint blockers, antibodies, nanoparticles) within 42 days before the first dose of IP

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 (PGP) activity within 14 days before the first dose of CT7001

18. Receipt of a blood transfusion (blood or blood products) within 14 days before the first dose of IP

19. Known hypersensitivity to CT7001 or any excipient of the product

20. Impaired hepatic or renal function as demonstrated by any of the following laboratory values:

1. Albumin < 30 g/L

2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × the upper limit of normal (ULN)

3. > 5.0 × ULN for patients with liver metastases

4. Total bilirubin > 1.5 × ULN

5. Serum creatinine > 1.5 × ULN

21. Liver function deteriorating in a manner that would likely make the participant meet the AST, ALT, or bilirubin levels specified above at the time of the first dose of IP

22. Other evidence of impaired hepatic synthesis function

23. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

1. Absolute neutrophil count (ANC) < 1.5 × 10^9/L

2. Platelet count < 100 × 10^9/L

3. Haemoglobin < 90 g/L

24. Persistent (> 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC < 0.5 × 10^9/L or platelets < 50 x 10^9/L)

25. Cardiac dysfunction (defined as myocardial infarction within 6 months of study entry, New York Heart Association Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias, or left ventricular ejection fraction < 55 percent)

26. Mean resting QT interval corrected for heart rate by the Fridericia formula (QTcF) > 470 msec obtained from 3 electrocardiograms (ECGs) obtained within 5 minutes of each other prior to the first dose

27. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (e.g., complete left bundle branch block, third degree heart block). Controlled atrial fibrillation (AF) is permitted

28. Any factor that increases the risk of QTc prolongation or of arrhythmic events (e.g., heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age)

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

1. International normalised ratio (INR) ≥1.5

1. No more than three lines of cytotoxic chemotherapy for metastatic/locally advanced disease

2. No advanced, symptomatic visceral metastases

3. No known symptomatic central nervous system (CNS) metastases, carcinomatous meningitis or leptomeningeal disease

4. Prior exposure to CT7001

5. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Carrick employees directly involved in the conduct of the trial

1. Prior therapy with fulvestrant

2. More than 2 lines of endocrine treatment for locally advanced or metastatic disease

3. Prior treatment with more than one line of cytotoxic chemotherapy for locally advanced or metastatic breast cancer.

4. Patients with liver metastasis will be limited to approximately 30-40% of the enrolled patients. l

5. Known hypersensitivity to CT7001, fulvestrant or any excipient of the investigational products

6. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Carrick employees directly involved in the conduct of the trial

1. Patients who were unable to fast for at least 10 hours

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Carrick Therapeutics Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew Krebs, MBChB PhD

Role: PRINCIPAL_INVESTIGATOR

The Christie Hospital, Manchester, UK

Locations

Research Site 54

Tucson, Arizona, United States

Research Site 31

Beverly Hills, California, United States

Research Site 37

Tampa, Florida, United States

Research Site 38

Chicago, Illinois, United States

Research Site 34

Boston, Massachusetts, United States

Research Site 47

Cincinnati, Ohio, United States

Research Site 39

Columbus, Ohio, United States

Research Site 36

Portland, Oregon, United States

Research Site 44

Austin, Texas, United States

Research Site 46

Dallas, Texas, United States

Research Site 48

Salt Lake City, Utah, United States

Research Site 33

Salem, Virginia, United States

Research site 11

Brighton, , United Kingdom

Research site 5

Cambridge, , United Kingdom

Research Site 7

Glasgow, , United Kingdom

Research Site 10

Liverpool, , United Kingdom

Research Site 9

London, , United Kingdom

Research Site 8

London, , United Kingdom

Research Site 3

London, , United Kingdom

Research Site 1

Manchester, , United Kingdom

Research Site 4

Manchester, , United Kingdom

Research Site 2

Oxford, , United Kingdom

Research Site 6

Southampton, , United Kingdom

Countries

United States; United Kingdom

References

Coombes RC, Howell S, Lord SR, Kenny L, Mansi J, Mitri Z, Palmieri C, Chap LI, Richards P, Gradishar W, Sardesai S, Melear J, O'Shaughnessy J, Ward P, Chalasani P, Arkenau T, Baird RD, Jeselsohn R, Ali S, Clack G, Bahl A, McIntosh S, Krebs MG. Dose escalation and expansion cohorts in patients with advanced breast cancer in a Phase I study of the CDK7-inhibitor samuraciclib. Nat Commun. 2023 Jul 24;14(1):4444. doi: 10.1038/s41467-023-40061-y.

Reference Type: DERIVED

PMID: 37488191 (View on PubMed)

Sava GP, Fan H, Coombes RC, Buluwela L, Ali S. CDK7 inhibitors as anticancer drugs. Cancer Metastasis Rev. 2020 Sep;39(3):805-823. doi: 10.1007/s10555-020-09885-8.

Reference Type: DERIVED

PMID: 32385714 (View on PubMed)

Other Identifiers

2017-002026-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CT7001_001

Identifier Type: -

Identifier Source: org_study_id