This is a modular, Phase I/II, multicentre study to investigate the optimal monotherapy dose
of CT7001 in advanced solid malignancies (Module 1A) and to further investigate the
monotherapy dose of CT7001 in specific participant groups (Module 1B). Further modules will
be added as substantial protocol amendments. A food-effect study of CT7001 monotherapy in
advanced solid malignancies (Module 4) is ongoing. A study of combination doses of CT7001
with fulvestrant in hormone receptor-positive (HR+ve) / human epidermal growth factor-2
negative (HER2-ve) breast cancer (Module 2) is planned to start in 2019.
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. Part A has now completed recruitment (39
participants dosed) and has identified the MBAD as 120mg once daily and the MTD as 360mg
once daily. The recommended dose to take forward to Phase II is 360mg.
- Part B: To refine the safety, tolerability, and PK and PD profiles of CT7001 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) will recruit up to 50
participants treated with a 360mg daily dose of CT7001 as monotherapy. Recruitment
is currently open.
- Part B, Cohort 2, Prostate Cancer (M1B-2 CRPC) will recruit up to 25 participants
treated with a 360mg daily dose of CT7001 as monotherapy. Recruitment is not yet
open.
- Additional Module 1B Cohorts of up to 25 participants each may be added in the
future.
Module 4 is a study investigating the effect of food on the PK of CT7001 monotherapy in
participants with advanced solid malignancies. Up to 24 participants will be recruited.
Recruitment is currently open.
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 will recruit up to 75 participants and will dose CT7001 in
combination with fulvestrant. Part B will be single-blind, randomized and placebo-controlled.
Core 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 12 months (Module 2) after the last dose of CT7001
5. Men, if sexually active, must be willing to use condoms 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
Core 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 cytotoxic treatment for the malignancy within 28 days 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
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
6. International normalised ratio (INR) ≥ 1.5
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
Additional Module 1A Inclusion Criteria:
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 biopsy
Additional Module 1B Inclusion Criteria
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
Additional Module 1B-1 (TNBC Expansion) Inclusion Criteria:
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
chemotherapy
3. Disease measurable by RECIST v1.1
4. Must have received prior cytotoxic chemotherapy with a taxane and an anthracycline
5. Must have received at least one cytotoxic chemotherapy for metastatic/locally advanced
disease
Additional Module 1B-1 (TNBC Expansion) Exclusion Criteria:
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
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
Additional Module 2 Inclusion Criteria:
1. Women only
2. Pre- or peri-menopausal women must have initiated goserelin at least 28 days prior to
first dose of CT7001/placebo
3. Histologically-confirmed, metastatic or locally advanced, ER+ve and/or PG+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 for locally advanced or metastatic disease
or for treatment of early breast cancer if the disease-free interval was <12 months
7. Must have received a CDK4/6 inhibitor for locally advanced or metastatic breast cancer
Additional Module 2 Exclusion Criteria:
1. Prior therapy with fulvestrant
2. More than 2 lines of endocrine treatment for locally advanced or metastatic disease
3. Known hypersensitivity to CT7001, fulvestrant or any excipient of the investigational
products
4. 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
Additional Module 4 Inclusion Criteria:
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
Additional Module 4 Exclusion Criteria:
1. Patients who were unable to fast for at least 10 hours
