CINATRA: Chromosomal Instability and Anti-Tubulin Response Assessment

ISRCTN ISRCTN58864837
DOI https://doi.org/10.1186/ISRCTN58864837
Secondary identifying numbers CCR 2983
Submission date
05/03/2008
Registration date
21/04/2008
Last edited
25/10/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-patupilone-for-people-with-advanced-bowel-cancer

Contact information

Dr Ian Chau
Scientific

Department of Medicine
Royal Marsden Hospital
Downs Road
Sutton
SM2 5PT
United Kingdom

Study information

Study designPhase II single-arm interventional study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please contact Dr Angela Gillbanks at Angela.Gillbanks@rmh.nhs.uk to request a patient information sheet
Scientific titleA phase 2 study of Epo906/patupilone in metastatic colorectal carcinoma in patients with microsatellite instability or chromosomal instability previously treated with irinotecan, oxaliplatin and fluoropyrimidines
Study acronymCINATRA
Study objectivesTo determine the anti-tumour activity of Epo906 administered to patients with metastatic colorectal cancer previously treated with irinotecan, oxaliplatin and fluoropyrimidines.

As of 19/03/2009 this record has been updated to include an amended overall trial start date; the initial start date at the time of registration was 01/05/2008.
Ethics approval(s)Hertfordshire Research Ethics Committee, 13/05/2008
Health condition(s) or problem(s) studiedMetastatic colorectal cancer
InterventionThis trial aims to find out whether Epo906 has activity in the two main types of colorectal cancer: cancers with a near normal DNA content (i.e. unselected patients [Cohort A]; microsatellite instability) and cancers with a continuously changing DNA content (Cohort B; chromosomal instability). The first part of the trial will assess the activity of Epo906 in all patients (Cohort A). In the second part of the study, only patients who have tumours with a near normal DNA content will be treated (Cohort B).

Cohort A (75 unselected patients; microsatellite instability): Epo906/patupilone is given intravenously (iv) at a dose of 8 mg/m^2 over 20 minutes on day 1 of a 21-day cycle, after pre-medication with iv dexamethasone and metoclopramide. Patients will receive 8 cycles (8 doses) unless there is evidence of disease progression or unacceptable toxicity.

Cohort B (35 patients selected for microsatellite instability): As above
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Epo906/patupilone
Primary outcome measureTwelve-week progression free survival (PFS). This will be measured by comparing a CT scan of the thorax/abdomen and pelvis at baseline (Within 28 days of starting treatment) to a second CT scan performed after 12 weeks from trial registration, evaluated by RECIST criteria.
Secondary outcome measures1. To determine the effect of CIN and MSI on the efficacy (response rate and progression-free survival [PFS]) of Epo906 as an anticancer agent, assuming that MSI+ colorectal cancer patients will benefit more than CIN+ colorectal cancer patients
2. To describe the safety of Epo906 and quality of life benefits associated with treatment
3. To correlate specific genetic variation with outcome following EPO906 therapy, in particular with reference to adenomatous polyposis coli (APC) gene status (MSI+ APCwt versus MSI APCmutant versus CIN). Other genetic analysis will include but not be limited to, b-catenin, Kras, or Braf mutations; copy number polymorphisms; loss of heterozygosity (LOH)
4. To retrospectively assess the response to prior treatment in relation to MSI and CIN status, particularly with reference to response to irinotecan and oxaliplatin containing regimens

The following assessments will be carried out:
a. Overall survival (Time from trial registration to death from any cause), response rate (Proportion of patients with complete or partial response as their best response as measured by RECIST criteria), tumour control rate (Total number of patients with best response measured by RECIST criteria as complete response, partial response or stable disease)
b. Twelve-week PFS stratified by MSI and CIN status, tested by flow immunohistochemistry, flow cytometry and DNA analysis of tumour sample
c. Response rate stratified by MSI and CIN status, tested by flow immunohistochemistry, flow cytometry and DNA analysis of tumour sample
d. Incidence of serious toxicity with Epo906 therapy, measured by CTCAE version 3.0
e. Quality of life parameters, measured by EORTC QLQ-C30 and QLQ-CR38 questionnaires at baseline, prior to cycles 2 and 5 and at the end of treatment
f. To retrospectively assess response to prior treatments according to MSI and CIN status, tested by flow immunohistochemistry, flow cytometry and DNA analysis of tumour sample
Overall study start date17/11/2008
Completion date01/05/2012

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants110
Total final enrolment29
Key inclusion criteria1. Male or female
2. 18 years of age or older
3. Histologically confirmed metastatic or locally recurrent carcinoma of the colon or rectum
4. Prior therapy with oxaliplatin, a fluoropyrimidine, and irinotecan for colorectal cancer. If a patient has previously received raltitrexed, this would be considered as equivalent to fluoropyrimidine treatment
5. Availability of paraffin embedded tumour tissue for analysis of microsatellite instability (MSI) status and chromosomal instability (CIN)
6. Life expectancy of 12 weeks or greater
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
8. Clinically and/or radiographically documented measurable disease according to the Response Evaluation Criteria In Solid Tumours (RECIST), with at least one unidimensionally lesion measuring 10mm or greater by spiral CT or 20mm or greater by conventional (non-spiral) computerised tomography (CT)
9. Adequate liver function:
9.1. Serum aspartate aminotransferase (AST) less than or equal to 5 x upper limit of normal (ULN)
9.2. Serum alanine aminotransferase (ALT) less than or equal to 5 x ULN
9.3. Serum alkaline phosphatase (ALP) less than 5 x ULN
9.4. Total serum bilirubin less than 1.5 x ULN
9.5. Prothrombin time (PT) less than or equal to 1.5 x ULN
10. Adequate haematological function:
10.1. Absolute neutrophil count (ANC) greater than or equal to 1.0 x 10^9/L
10.2. Platelets greater than or equal to 100 x 10^9/L
10.3. Haemoglobin greater than or equal to 9.0 g/dL
11. Serum creatinine clearance of greater than 50 ml/min according to the Cockcroft-Gault calculation or measured glomerular filtration rate of greater than 50 ml/min
12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
13. Prior radiotherapy or colostomy are allowed. A marker lesion may not be in a previously irradiated area, unless there has been documented disease progression in that area since radiotherapy.
14. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects prior to enrolment
15. For Cohort B, all patients must have tumours which are microsatellite instability (MSI) positive by immunohistochemistry (IHC)
16. Patients must be willing to undertake adequate contraceptive methods or remain sexually abstinent for the duration of study treatment and for at least 28 days after receiving the last dose of study drug
Key exclusion criteria1. Persistent toxicity from previous treatment. Neurotoxicity from prior oxaliplatin must have resolved to at least grade 1.
2. Diagnosis of or treatment for any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell carcinoma of the skin, or adequately treated in-situ cervical cancer
3. Any of the following within the 12 months prior to study drug administration:
3.1. Myocardial infarction or severe/unstable angina
3.2. Coronary/peripheral artery bypass graft
3.3. Symptomatic congestive heart failure
3.4. Cerebrovascular accident or transient ischaemic attack
3.5. Pulmonary embolism
4. Pregnancy or breastfeeding
5. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
6. Clinically significant neuropathy that could be worsened by study treatment
Date of first enrolment10/12/2008
Date of final enrolment01/05/2010

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Royal Marsden Hospital
Sutton
SM2 5PT
United Kingdom

Sponsor information

The Royal Marsden Hospital NHS Foundation Trust (UK)
Hospital/treatment centre

Downs Road
Sutton
SM2 5PT
England
United Kingdom

Phone +44 (0)208 6613279
Email angela.gillbanks@rmh.nhs.uk
ROR logo "ROR" https://ror.org/0008wzh48

Funders

Funder type

Government

The Royal Marsden Hospital NHS Foundation Trust (UK)

No information available

Novartis Pharmaceuticals (UK) - supported in conjunction with Professor Cunningham's Charitable Research Fund (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/10/2013 Yes No
Plain English results 25/10/2022 No Yes

Editorial Notes

25/10/2022: Cancer Research UK plain English results link and total final enrolment added.