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Trial record 1 of 1 for:    NCT02797977
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A Phase I Trial of CCT245737 in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Alone 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:
NCT02797977
First received: May 23, 2016
Last updated: January 9, 2017
Last verified: January 2017
  Purpose

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 which can make cells produce chemicals that trigger and control cell growth and cell death. Chemotherapy agents are used to try to kill cancer cells however sometimes cancer cells can repair themselves using these signaling processes and continue to grow. It is thought that CCT245737 may help chemotherapy to work better by preventing cancer cells from repairing themselves, when they have been damaged by the chemotherapy, so that more cancer cells will be killed.

There are 2 stages to this study:

  1. Patients in Stage 1 will be given CCT245737 to take in addition to receiving treatment with gemcitabine and cisplatin.
  2. Patients in Stage 2 will be given CCT245737 to take in addition to receiving treatment with gemcitabine only.

The main aims of the study are to find the maximum dose of CCT245737 that can be given safely to patients with gemcitabine and cisplatin or gemcitabine alone, more about the potential side effects of the drugs and how they can be managed and what happens to the combination of drugs inside the body.


Condition Intervention Phase
Advanced Solid Tumours
Non-small Cell Lung Cancer
Pancreatic Cancer
Drug: CCT245737
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Oral CCT245737 (a CHK1 Inhibitor) Given in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Alone 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 administered in combination with gemcitabine +/- cisplatin assessed as the incidence, severity and causality of adverse events [ Time Frame: Up to 28 days after last dose of CCT245737 ]
  • To propose a recommended Phase II dose of CCT245737 administered in combination with gemcitabine +/- cisplatin [ Time Frame: Up to 28 days after last dose of CCT245737 ]
    A recommended Phase II dose of CCT245737 administered in combination with gemcitabine +/- cisplatin 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 the plasma levels of CCT245737 to define the maximum observed plasma concentration (Cmax) [ Time Frame: 48 hour time course after the first dose of CCT2456737 and again for 48 hours after dosing on Cycle 1 Day 2. ]
    Pharmacokinetic profile of CCT245737 administered in combination with gemcitabine +/- cisplatin.

  • Assessment of the plasma levels of CCT245737 to define the terminal elimination half-life (Tmax) [ Time Frame: 48 hour time course after the first dose of CCT2456737 and again for 48 hours after dosing on Cycle 1 Day 2. ]
    Pharmacokinetic profile of CCT245737 administered in combination with gemcitabine +/- cisplatin.

  • Assessment of the plasma levels of CCT245737 to define the area under the curve (AUC) [ Time Frame: 48 hour time course after the first dose of CCT2456737 and again for 48 hours after dosing on Cycle 1 Day 2. ]
    Pharmacokinetic profile of CCT245737 administered in combination with gemcitabine +/- cisplatin.

  • Assessment of the plasma levels of CCT245737 to define the terminal elimination half-life (T1/2) [ Time Frame: 48 hour time course after the first dose of CCT2456737 and again for 48 hours after dosing on Cycle 1 Day 2. ]
    Pharmacokinetic profile of CCT245737 administered in combination with gemcitabine +/- cisplatin.


Estimated Enrollment: 70
Study Start Date: June 2016
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Stage 1
CCT245737 will be administered orally on Day -7 to -4 and Days 2, 3, 9 and 10 of each 21 day cycle
Drug: CCT245737
Stage 1: CCT245737 will be administered orally on Day -7 to -4 as a single dose and then on Days 2, 3, 9 and 10 of each 21 days cycle. Gemcitabine will be administered via IV infusion on Days 1 and 8 and cisplatin on Day 1 of each cycle. A maximum of 6 cycles may be given.
Stage 2
CCT245737 will be administered orally on Day -7 to -4 and Days 2, 3, 9, 10, 16 & 17 of each 28 day cycle
Drug: CCT245737
Stage 2: CCT245737 will be administered orally on Day -7 to -4 as a single dose and then on Days 2, 3, 9, 10 16 & 17 of each 28 days cycle. Gemcitabine will be administered via IV infusion on Days 1, 8, and 15 of each cycle. A maximum of 8 cycles may be given.

Detailed Description:
Each stage of the study is split into two parts: Part one will be a 'dose escalation' phase where cohorts of 3 to 6 patients will receive increasing doses of CCT245737 until the recommended Phase II dose is established. Part two will be an 'expansion phase' where a larger group of patients will be treated at the recommended Phase II dose to find out more about how the drug is working. In the Stage 1 dose expansion part, patients with either solid tumours amenable to biopsy or non-small cell lung cancer will be recruited. In the Stage 2 dose expansion part patients with either solid tumours amenable to biopsy or pancreatic cancer will be recruited.
  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 where treatment with gemcitabine plus cisplatin or gemcitabine alone is considered appropriate by the Investigator.
  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 Renal function for Stage 1 (CCT245737 + gemcitabine + cisplatin schedule)

    Either:

    Calculated creatinine clearance by Cockroft ≥ 60 mL/min and Gault formula

    Or:

    Isotope clearance measurement ≥ 60 mL/min (uncorrected value)

    Renal function for Stage 2 (CCT245737 + ≤ 1.5 x upper limit of normal (ULN) Gemcitabine schedule)

    Serum Creatinine

    QTcF Equal to or less than 450 msec

  6. 18 years or over at the time consent is given.
  7. Expansion Cohort at MTD: Patients must give consent for and have disease amenable to paired biopsies in all solid tumour cohorts (Optional for NSCLC and Pancreatic Cancer cohorts).

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, immunotherapy or chemotherapy during the previous four weeks, immunotherapy during the previous four weeks, nitrosoureas or Mitomycin-C during the previous six weeks and investigational medicinal products (IMPs) during the previous four weeks before treatment. Patients with prostate cancer can continue treatment with luteinising hormone release hormone (LHRH) analogues.
  2. No more than three previous lines of cytotoxic chemotherapy for metastatic disease.
  3. If, in the opinion of the Investigator, the patient is highly likely to experience clinically significant myelosuppression, based on previous experience with chemotherapy.
  4. Ongoing toxic manifestations of previous treatments greater than CTCAE Grade 1. Exceptions to this are alopecia and any ongoing toxic manifestation which in the opinion of the Investigator and the CDD Medical Advisor should not exclude the patient.
  5. Clinical significant hearing impairment.
  6. History of allergy to cisplatin or other platinum containing compounds, to gemcitabine, or to the excipients in these products.
  7. New or progressing brain metastases. Patients with brain metastases that have been radiologically stable over an 8 week period may be included.
  8. Female patients who are able to become pregnant (or 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 to sexual abstinence, effective from the first administration of CCT245737, throughout the trial and for six months afterwards are considered eligible.
  9. 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 to the foetus or neonate.
  10. Major thoracic or abdominal surgery from which the patient has not yet recovered.
  11. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
  12. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus.
  13. 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
  14. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks.
  15. Peanut allergy
  16. 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.
  17. 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: NCT02797977

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 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: NCT02797977     History of Changes
Other Study ID Numbers: PNT737-02 
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
non-small cell lung cancer
pancreatic cancer
Phase I
Dose escalation
CHK1 inhibitor
checkpoint kinase 1

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 24, 2017