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

Sponsor
Carrick Therapeutics Limited (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03363893
Collaborator
(none)
250
Enrollment
31
Locations
8
Arms
63.5
Anticipated Duration (Months)
8.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: CT7001
  • Drug: CT7001 in combination with fulvestrant
  • Drug: CT7001 (in original vs enteric capsule)
 Phase 1/Phase 2

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. Recruitment 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.

  • 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. Recruitment 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 will dose CT7001 in combination with fulvestrant. Module 2 consists of 3 parts - Part A, Part B and Part C. Module 2 Part A recruitment is completed.Part B is double-blind, randomized and placebo-controlled Part C will be a crossover from Part B. Module 2B/C is planned to open in 2022.

  • Module 6 is 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Modular designModular design
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Modular, Multipart, Multiarm, Open-label, Phase I/II Study to Evaluate the Safety and Tolerability of CT7001 Alone and in Combination With Anti-cancer Treatments in Patients With Advanced Malignancies
Actual Study Start Date :
Nov 14, 2017
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Module 1 Part A

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). This module includes a cohort expansion of participants with breast cancer who provide paired biopsy samples.

Drug: CT7001
Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression
Other Names:
  • Samuraciclib

    		•
    Experimental: Module 1 Part B

    Participants with advanced solid tumours that may include, but is not limited to, triple negative breast cancer (TNBC), castrate-resistant prostate cancer (CRPC), small cell lung cancer (SCLC) or ovarian cancer, will receive CT7001 (samuraciclib) as oral monotherapy at the dose, frequency and schedule recommended from Module 1 Part A. To date Module 1 Part B Arm has recruited a cohort of CRPC participants.

    Drug: CT7001
    Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression
    Other Names:
  • Samuraciclib

    		•
    Experimental: Module 1 Part B-1 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.

    Drug: CT7001
    Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression
    Other Names:
  • Samuraciclib

    		•
    Experimental: Module 2 Part A

    Participants with locally advanced or metastatic HR+ve and HER2-ve breast cancer will receive CT7001 (samuraciclib) oral monotherapy in combination with fulvestrant.

    Drug: CT7001 in combination with fulvestrant
    Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression in combination with fulvestrant given as 2 x 250mg intramuscular (IM) gluteal injections on Day 1, Day 15, Day 28 and every 28 days thereafter
    Other Names:
  • Samuraciclib

    		•
    Experimental: Module 2 Part B

    Participants with locally advanced or metastatic HR+ve and HER2-ve breast cancer will be randomized to receive CT7001 (samuraciclib) or matching placebo as oral monotherapy at the dose determined in Module 2 Part A, in combination with fulvestrant.

    Drug: CT7001 in combination with fulvestrant
    Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression in combination with fulvestrant given as 2 x 250mg intramuscular (IM) gluteal injections on Day 1, Day 15, Day 28 and every 28 days thereafter
    Other Names:
  • Samuraciclib

    		•
    Experimental: Module 2 Part C

    Participants with locally advanced or metastatic HR+ve and HER2-ve breast cancer who were enrolled to the placebo arm in Module 2 Part B will, on progression of disease, receive CT7001 (samuraciclib) oral monotherapy in combination with fulvestrant.

    Drug: CT7001 in combination with fulvestrant
    Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression in combination with fulvestrant given as 2 x 250mg intramuscular (IM) gluteal injections on Day 1, Day 15, Day 28 and every 28 days thereafter
    Other Names:
  • Samuraciclib

    		•
    Experimental: 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.

    Drug: CT7001
    Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression
    Other Names:
  • Samuraciclib

    		•
    Experimental: Module 6

    Participants with advanced solid malignancies will receive CT7001 (samuraciclib) and a new enteric capsule CT7001 (EC) (samuraciclib) oral monotherapy in a randomized, single blind, balanced, two treatment two period, two sequence crossover with one wash out period in between, followed by once daily continuous dosing.

    Drug: CT7001 (in original vs enteric capsule)
    Cyclin-dependent kinase 7 (CDK7) inhibitor given orally once daily until disease progression
    Other Names:
  • Samuraciclib

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability) [Screening to end of study]

      Type, incidence and severity

    Secondary Outcome Measures

    1. Maximum Plasma Concentration of CT7001 (and Fulvestrant, where applicable) (Cmax) [After the first dose and during the dosing period]

    2. Area Under the Curve (AUC) [After the first dose and during the dosing period]

    3. Biological Activity Parameters (Biomarkers) in Peripheral Blood [Screening to end of treatment]

    4. Anti-tumour Activity according to RECIST v1.1 [Baseline until disease progression or withdrawal from the study]

    5. Objective Response Rate (ORR) [Baseline until disease progression or withdrawal from the study]

    6. Progression-Free Survival (PFS) [Baseline until disease progression or withdrawal from the study]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 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

    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 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:

    21. Albumin < 30 g/L

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

    23. 5.0 × ULN for patients with liver metastases

    24. Total bilirubin > 1.5 × ULN

    25. Serum creatinine > 1.5 × ULN

    26. 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

    27. Other evidence of impaired hepatic synthesis function

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

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

    30. Platelet count < 100 × 10^9/L

    31. Haemoglobin < 90 g/L

    32. Persistent (> 4 weeks) severe pancytopenia due to previous therapy rather than to disease (ANC < 0.5 × 109/L or platelets < 50 x 109/L)

    33. 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)

    34. 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

    35. 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

    36. 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)

    37. In the opinion of the Investigator, unlikely to comply with study procedures, restrictions, or requirements

    38. A history of haemolytic anaemia or marrow aplasia

    39. 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 repeat biopsy

    Additional Module 1A Exclusion Criteria:
    1. International normalised ratio (INR) ≥1.5

    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 prior cytotoxic chemotherapy

    3. Disease measurable by RECIST v1.1

    4. 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 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

    Additional Module 2 Inclusion Criteria:

    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. Part A only: 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. For Part B only: patients must have received at least 6 months clinical benefit with the CDK4/6 as a line of therapy immediately preceding study entry. Patients who received CDK4/6 inhibitor < 6 months due to tolerability issues when at least 6 months aromatase inhibitor was received.

    8. Ability to receive intramuscular injections.

    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. Part A Only: Prior treatment with more than one line of cytotoxic chemotherapy for locally advanced or metastatic breast cancer.

    4. Part B Only: Prior treatment with cytotoxic chemotherapy for locally advanced or metastatic breast cancer or treatment with a mammalian target of rapamycin (mTOR) inhibitor including, but not limited to, everolimus.

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

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

    7. 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
    Additional Module 6 Inclusion Criteria:
    1. Histological, radiological or cytological confirmation of an advanced non- haematological malignancy not considered to be appropriate for further standard treatment.
    Additional Module 6 Exclusion Criteria:

    1. Any concurrent gastrointestinal conditions, not covered in Core Protocol Exclusion Criteria #4

    2. Patients whom has received an agent that increases gastric pH (i.e. proton pump inhibitors (PPI), H2 antagonists) within 2 days or 5 half-lives, whichever is shorter, prior to PK Period Day 1.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site 42 Tucson Arizona United States 85704
    2 Research Site 54 Tucson Arizona United States 85719
    3 Research Site 31 Beverly Hills California United States 90211
    4 Research Site 37 Tampa Florida United States 33612
    5 Research Site 49 Augusta Georgia United States 30912
    6 Research Site 38 Chicago Illinois United States 60611
    7 Research Site 34 Boston Massachusetts United States 02215
    8 Research Site 55 New York New York United States 10065
    9 Research Site 47 Cincinnati Ohio United States 45236
    10 Research Site 39 Columbus Ohio United States 43212
    11 Research Site 36 Portland Oregon United States 97239
    12 Research Site 43 Charleston South Carolina United States 29414
    13 Research Site 44 Austin Texas United States 78705
    14 Research Site 46 Dallas Texas United States 75246
    15 Research Site 51 Fort Worth Texas United States 76086
    16 Research Site 48 Salt Lake City Utah United States 84112
    17 Research Site 41 Norfolk Virginia United States 23502
    18 Research Site 33 Salem Virginia United States 24153
    19 Research site 11 Brighton United Kingdom BN2 5BE
    20 Research site 5 Cambridge United Kingdom CB2 0QQ
    21 Research Site 7 Glasgow United Kingdom G12 0YN
    22 Research Site 12 Guildford United Kingdom GU2 7XX
    23 Research Site 13 Leicester United Kingdom LE1 5WW
    24 Research Site 10 Liverpool United Kingdom L69 3BX
    25 Research Site 9 London United Kingdom SE1 9RT
    26 Research Site 8 London United Kingdom W1G 6AD
    27 Research Site 3 London United Kingdom W2 1NY
    28 Research Site 1 Manchester United Kingdom M20 4BX
    29 Research Site 4 Manchester United Kingdom M20 4BX
    30 Research Site 2 Oxford United Kingdom OX3 7LE
    31 Research Site 6 Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • Carrick Therapeutics Limited

    Investigators

    • Principal Investigator: Matthew Krebs, MBChB PhD, The Christie Hospital, Manchester, UK

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Carrick Therapeutics Limited
    ClinicalTrials.gov Identifier:
    NCT03363893
    Other Study ID Numbers:
    • CT7001_001
    • 2017-002026-20
    First Posted:
    Dec 6, 2017
    Last Update Posted:
    Nov 30, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Carrick Therapeutics Limited
    Neoplasms
    Additional relevant MeSH terms:
    Neoplasms
    Fulvestrant

    Study Results

    No Results Posted as of Nov 30, 2021