Clinical Trials /

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

NCT03363893

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Prostate Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Modular Study to Evaluate CT7001 Alone in Cancer Patients With Advanced Malignancies
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CT7001_001
  • NCT ID: NCT03363893

Conditions

  • Advanced Solid Malignancies

Interventions

DrugSynonymsArms
CT7001Module 1 Part A
CT7001 in combination with fulvestrantModule 2 Part A

Purpose

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.

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. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Module 1 Part AExperimentalParticipants with advanced solid tumours receive CT7001 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).
  • CT7001
Module 1 Part BExperimentalParticipants with advanced solid tumours that may include, but is not limited to, castrate-resistant prostate cancer (CRPC), small cell lung cancer (SCLC) or ovarian cancer, will receive CT7001 as oral monotherapy at the dose, frequency and schedule recommended from Module 1 Part A.
  • CT7001
Module 1 Part B-1 TNBC ExpansionExperimentalParticipants with locally advanced or metastatic triple-negative breast cancer (TNBC) will receive CT7001 as oral monotherapy at the dose, frequency and schedule recommended from Module 1 Part A.
  • CT7001
Module 2 Part AExperimentalParticipants with locally advanced or metastatic HR+ve and HER2-ve breast cancer will receive CT7001 oral monotherapy at either 240mg (Cohort 1) or 360mg (Cohort 2) in combination with fulvestrant.
  • CT7001 in combination with fulvestrant
Module 2 Part BExperimentalParticipants with locally advanced or metastatic HR+ve and HER2-ve breast cancer will be randomized to receive CT7001 or matching placebo as oral monotherapy at the dose determined in Module 2 Part A, in combination with fulvestrant.
  • CT7001 in combination with fulvestrant
Module 2 Part CExperimentalParticipants 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 oral monotherapy in combination with fulvestrant.
  • CT7001 in combination with fulvestrant
Module 4ExperimentalParticipants with advanced solid tumours will receive CT7001 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.
  • CT7001

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment-Emergent Adverse Events and Laboratory Abnormalities (Safety and Tolerability)
Time Frame:Screening to end of study
Safety Issue:
Description:Type, incidence and severity

Secondary Outcome Measures

Measure:Maximum Plasma Concentration of CT7001 (and Fulvestrant, where applicable) (Cmax)
Time Frame:After the first dose and during the dosing period
Safety Issue:
Description:
Measure:Area Under the Curve (AUC)
Time Frame:After the first dose and during the dosing period
Safety Issue:
Description:
Measure:Biological Activity Parameters (Biomarkers) in Peripheral Blood
Time Frame:Screening to end of treatment
Safety Issue:
Description:
Measure:Anti-tumour Activity according to RECIST v1.1
Time Frame:Baseline until disease progression or withdrawal from the study
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Baseline until disease progression or withdrawal from the study
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS)
Time Frame:Baseline until disease progression or withdrawal from the study
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Carrick Therapeutics Limited

Trial Keywords

  • Neoplasms

Last Updated

June 6, 2019