Condition category
Cancer
Date applied
05/03/2008
Date assigned
21/04/2008
Last edited
20/07/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Ian Chau

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CCR 2983

Study information

Scientific title

A 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

Acronym

CINATRA

Study hypothesis

To 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

Hertfordshire Research Ethics Committee, 13/05/2008

Study design

Phase II single-arm interventional study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please contact Dr Angela Gillbanks at Angela.Gillbanks@rmh.nhs.uk to request a patient information sheet

Condition

Metastatic colorectal cancer

Intervention

This 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 type

Drug

Phase

Not Applicable

Drug names

Epo906/patupilone

Primary outcome measures

Twelve-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 measures

1. 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 trial start date

17/11/2008

Overall trial end date

01/05/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

110

Participant exclusion criteria

1. 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

Recruitment start date

10/12/2008

Recruitment end date

01/05/2010

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Marsden Hospital
Sutton
SM2 5PT
United Kingdom

Sponsor information

Organisation

The Royal Marsden Hospital NHS Foundation Trust (UK)

Sponsor details

Downs Road
Sutton
SM2 5PT
United Kingdom
+44 (0)208 6613279
angela.gillbanks@rmh.nhs.uk

Sponsor type

Government

Website

Funders

Funder type

Government

Funder name

The Royal Marsden Hospital NHS Foundation Trust (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23801302

Publication citations

Additional files

Editorial Notes