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Trial record 2 of 2 for:    CCT245737

A Phase I Trial of CCT245737 in Patients With Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Sierra Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Sierra Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02797964
First received: May 23, 2016
Last updated: January 9, 2017
Last verified: January 2017
  Purpose

The main aims of this clinical study are to find out the maximum dose of CCT245737 that can be given safely to patients, more about the potential side effects of the drug and how they can be managed and what happens to CCT245737 inside the body.

CCT245737 is a type of drug called a kinase inhibitor. It blocks a chemical messenger (enzyme) called checkpoint kinase 1 (CHK-1) which is part of the signaling process within cells. This can make cells produce chemicals that trigger and control cell growth and cell death. In some types of cancer these chemical messengers are 'switched on' or 'switched off' allowing the cancer cells to keep growing and to grow more quickly than normal cells. Kinase inhibitors are a new type of drug being used to try to stop the growth of cancers and to kill cancer cells


Condition Intervention Phase
Advanced Solid Tumours
Drug: CCT245737
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of CCT245737 (a CHK1 Inhibitor) Administered Orally in Patients With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by Sierra Oncology, Inc.:

Primary Outcome Measures:
  • Safety and Tolerability of CCT245737 assessed as the incidence, severity and causality of adverse events [ Time Frame: Up to 28 days after last dose of CCT245737. ]
  • The highest dose at which ≤33% of patients have a dose limiting toxicity (DLT) in a cohort of up to 6 patients of CCT245737 [ Time Frame: Up to 28 days after last dose of CCT245737 ]
    A recommended safe dose of CCT245737 for evaluation in Phase II trials as defined by a dose at which no more than one patient out of up to six patients at the same dose level experience a highly probably or probably drug-related dose limiting toxicity (DLT).


Secondary Outcome Measures:
  • Assessment of plasma levels of CCT245737 to define the maximum observed plasma concentration (Cmax) [ Time Frame: 48 hrs after CCT245737 dose 1, C1D15 or C1D22 ]
    PK profiling will be measured over a 48 hour time course after the first dose of CCT2456737 and again for 48 hours after dosing on Cycle 1 Day 15 or 22.

  • Assessment of plasma levels of CCT245737 to define the time to reach Cmax (Tmax) [ Time Frame: 48 hrs after CCT245737 dose 1, C1D15 or C1D22 ]
    PK profiling will be measured over a 48 hour time course after the first dose of CCT2456737 and again for 48 hours after dosing on Cycle 1 Day 15 or 22.

  • Assessment of plasma levels of CCT245737 to define the area under the curve (AUC) [ Time Frame: 48 hrs after CCT245737 dose 1, C1D15 or C1D22 ]
    PK profiling will be measured over a 48 hour time course after the first dose of CCT2456737 and again for 48 hours after dosing on Cycle 1 Day 15 or 22.

  • Assessment of plasma levels of CCT245737 to define the terminal elimination half-life (T1/2) [ Time Frame: 48 hrs after CCT245737 dose 1, C1D15 or C1D22 ]
    PK profiling will be measured over a 48 hour time course after the first dose of CCT2456737 and again for 48 hours after dosing on Cycle 1 Day 15 or 22.


Estimated Enrollment: 40
Study Start Date: May 2016
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open label Drug: CCT245737
CCT245737 will be taken orally on each day of a 28 day cycle including a single dose within 4-7 days prior to the start of the first 28 day cycle. Patients may have up to 12 cycles if there is clinical benefit.

Detailed Description:
The study will follow a dose escalation design, initially with single patient cohorts until Grade 2 toxicity is observed, cohorts will then be expanded to 3-6 patients following a rolling six design until the maximum tolerated dose is reached. Six further patients with disease amenable to biopsy will then be treated at this dose level or below in order to establish the recommenced Phase II dose for further evaluation.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
  2. Histologically or cytologically proven solid tumour, refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the patient.
  3. Life expectancy of at least 12 weeks.
  4. World Health Organisation (WHO) performance status of 0-1 (Appendix 1).
  5. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week before the patient receives their first dose of IMP

    • Laboratory Test Value required
    • Haemoglobin (Hb) ≥ 90 g/L
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
    • Platelet count ≥ 100 x 10^9/L
    • Bilirubin ≤ 1.5 x upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and
    • Alkaline Phosphatase (ALP) ≤ 2.5 x ULN unless raised due to tumour in which case up to 5 x ULN is permissible
    • Serum Creatinine ≤ 1.5 x upper limit of normal (ULN)
  6. At least 18 years old at the time consent is given.
  7. Expansion Cohort at MTD: Patients must give consent for and have disease amenable to paired biopsies.

Exclusion Criteria:

  1. Radiotherapy within the last six weeks (except for symptom control and where the lesions will not be used as measurable disease) and endocrine therapy except for luteinizing hormone releasing hormone (LHRH) agonists for prostate cancer, or, for all patients, chemotherapy during the previous four weeks, immunotherapy during the previous six weeks, nitrosoureas or Mitomycin-C during the previous six weeks or other investigational medicinal products (IMPs) during the four weeks before treatment.
  2. Ongoing toxic manifestations of previous treatments greater than CTCAE Grade 1. Exceptions to this are alopecia or certain toxicities, which in the opinion of the Investigator and the Medical Advisor should not exclude the patient.
  3. New or progressing brain metastases. Patients with brain metastases that have been radiologically stable over an 8 week period may be included.
  4. Female patients who are able to become pregnant (or are already pregnant or lactating). However, those patients who have a negative serum or urine pregnancy test before enrolment and agree to use two forms of contraception (one highly effective form plus a barrier method) [oral; injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom] or agree to sexual abstinence, effective from the first administration of CCT245737, throughout the trial and for six months afterwards are considered eligible.
  5. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using a barrier method of contraception [condom plus spermicide] or to sexual abstinence effective from the first administration of CCT245737, throughout the trial and for six months afterwards. Men with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual abstinence).

    Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate.

  6. Major thoracic or abdominal surgery from which the patient has not yet recovered.
  7. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
  8. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
  9. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA] - refer to Appendix 3), prior history of cardiac ischaemia or prior history of cardiac arrhythmia.
  10. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within 8 weeks.
  11. Patients that have previously had other myelosuppressive drugs such as mitomycin C within the last 6 weeks.
  12. Peanut allergy.
  13. QTc > 450 msec in adult males and > 470msec in adult females.
  14. Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I study of CCT245737. Participation in an observational trial or interventional clinical trial which does not involve administration of an IMP and which would not place an unacceptable burden on the patient in the opinion of the Investigator and Medical Advisor would be acceptable.
  15. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02797964

Locations
United Kingdom
Royal Marsden Hospital Recruiting
Sutton, London, United Kingdom, SM2 5PT
Contact: Contact Person       Udai.Banerji@icr.ac.uk   
Principal Investigator: Udai Banerji, Dr         
Velindre Cancer Centre - Cardiff Recruiting
Cardiff, Whitchurch, United Kingdom, CF14 2TL
Contact: Rob Jones, Dr       Robert.Hugh.Jones@wales.nhs.uk   
Principal Investigator: Rob Jones, Dr         
Freeman Hospital Recruiting
Newcastle upon Tyne, United Kingdom, NE7 7DN
Contact: Elizabeth R Plummer       Ruth.Plummer@newcastle.ac.uk   
Principal Investigator: Elizabeth R Plummer         
Sponsors and Collaborators
Sierra Oncology, Inc.
  More Information

Responsible Party: Sierra Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02797964     History of Changes
Other Study ID Numbers: PNT737-01
Study First Received: May 23, 2016
Last Updated: January 9, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Sierra Oncology, Inc.:
Solid tumours
Phase I
Dose escalation
CHK1 inhibitor
checkpoint kinase 1

ClinicalTrials.gov processed this record on April 26, 2017