Metastatic Colorectal Cancer, Recurrent Colorectal Cancer
Conditions
Keywords
Colorectal cancer, Metastatic Colorectal cancer, Recurrent Colorectal cancer, FOLFIRI, AZD8931, Chemotherapy, EGFR
Brief summary
Recruitment to phase I of the PANTHER trial is complete. Phase II, is to evaluate the best overall response rate for AZD8931 + FOLFIRI treatment.
Detailed description
PANTHER is a registered phase I/phase II trial in patients with recurrent or metastatic colorectal cancer. The phase II part of the study will be a single arm trial. Patients will receive AZD8931 (an EGFR/ERBB inhibitor) in combination with FOLinic acid, Fluorouracil and IRInotecan (FOLFIRI), Treatment will be given in two-weekly cycles. Phase II's primary objective is to evaluate the Best overall response
Interventions
DRUGAZD8931
160 mg AZD8931 tablets, twice daily on days 1 - 4 of each 2-weekly cycle
DRUGIrinotecan
180 mg/m2 (IV infusion) of Irinotecan on day 1 of each 2-weekly cycle - can be given simultaneously with Folinic acid.
DRUGFolinic Acid
350 mg (IV infusion) of Folinic acid on day 1 of each 2-weekly cycle - can be given simultaneously with Irinotecan.
DRUGFluorouracil
400 mg/m2 (IV bolus) of Fluorouracil on day 1 of each 2-weekly cycle, to be given after completion of Irinotecan and Folinic acid.
Sponsors
Cancer Research UK
AstraZeneca
National Institute for Health Research, United Kingdom
University College, London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histopathological/cytological diagnosis of non-resectable, recurrent or metastatic colorectal cancer 2. Tumour with wild-type RAS 3. Measurable disease evaluated by RECIST criteria v1.1 4. WHO performance status 0 or 1 5. Age ≥ 16 6. Estimated life expectancy \> 3 months 7. Adequate haematological function: * Haemoglobin ≥100 g/L * Absolute neutrophil count ≥1.5 x 10\^9/L * Platelet count ≥100 x 10\^9/L 8. Adequate liver function: * Total bilirubin ≤1.5 x upper limit of normal (ULN) (except for patients with known documented cases of Gilbert's syndrome) * ALT, AST & ALP ≤2.5 x ULN in the absence of noted liver metastases * ALT, AST & ALP ≤5 x ULN in the presence of liver metastases 9. Adequate renal function: * Serum creatinine ≤1.5 x ULN * Calculated creatinine clearance ≥30 mL/min 10. Adequate biliary drainage (patients with stents are eligible) 11. Adequate venous access for collection of exploratory biological samples 12. Women of child-bearing potential must have a negative pregnancy test prior to study entry. Female patients and male patients with partners of child-bearing potential must agree to use an adequate contraception method, which must be continued for 6 months after completion of chemotherapy 13. Must be able to swallow AZD8931 tablets 14. Capable of giving written informed consent 15. The following prior therapy is allowed: * Surgery - patients may have undergone a non-curative operation or palliative bypass surgery only. Patients who have previously undergone curative surgery must have evidence of non-resectable disease relapse * Radiotherapy - for localised disease * Prior adjuvant chemotherapy - provided this was completed at least 6 months before trial entry
Exclusion criteria
1. Patients undergoing treatment with curative intent 2. Any prior treatment with agents targeting the ERBB pathway 3. Treatment with experimental drugs within 30 days or 5 half-lives of first dose of AZD8931 4. Previous palliative chemotherapy 5. Prior treatment with anthracyclines or mitoxantrone 6. Current disease or condition known to interfere with absorption, distribution, metabolism or excretion of drugs (including refractory nausea and vomiting, chronic gastrointestinal disease (e.g. inflammatory bowel disease), or significant bowel resection) 7. History of prior malignancy that will interfere with the response evaluation (exceptions listed in protocol) 8. Evidence of severe/uncontrolled systemic diseases or laboratory finding that makes it undesirable for the patient to participate in the trial 9. Evidence of active uncontrolled infection 10. Patients with clinically significant ascites and/or effusions 11. Regular use of anti-diarrhoeal 12. Pregnant or lactating women 13. Cardiac conditions (as detailed in the trial protocol) 14. Any psychiatric or other disorder (e.g. brain metastases) likely to impact the ability to give informed consent 15. Eye conditions (as detailed in the trial protocol) 16. Patients with chronic skin conditions e.g. acne rosacea, psoriasis, severe atopic eczema 17. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease 18. History or repeated unexplained episodes of syncope/dizziness 19. Known hypersensitivity to AZD8931, its excipients, or drugs in its class 20. The use of drugs/substances known to inhibit or induce CYP3A4 or CYP2D6, or those known to prolong QT interval, which cannot be discontinued for the duration of trial treatment 21. Patients with hereditary fructose intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best overall response | From registration to date of documented best response, assessed up to 36 months | Best overall response will be assessed according to RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the efficacy of AZD8931 plus FOLFIRI | Baseline to 12 weeks post treatment start | Percentage change in tumour size will be considered the best response only if a second assessment has been carried out which confirms SD at least four weeks after trial entry. Assessment will be determined using CT scans performed at baseline, 12 weeks after start of chemotherapy, then every 3 months until disease progression up to 3 years from registration/ randomisation |
| Progression Free Survival | From date of randomisation to date of documented disease progression or death from any cause, whichever comes first, assessed up to 3 years from date of registration/ randomisation | Progression-free survival time will be calculated from the date of trial entry to the date of documented progression, or death from any cause. In cases where progression is suspected and subsequently confirmed by scans, the date of documented suspected progression will be used. |
| Overall Survival | From date of registration/ randomisation until date of death or date of last follow-up assessment (up to 3 years from date of registration/ randomisation) | Overall survival time will be calculated from the date of trial entry to the date of death from any cause or end of trial follow-up. |
| Occurrence and Severity of Adverse Events | From date of registration/ randomisation until 30 days after completion of trial treatment (AZD8931 and FOLFIRI) | Will include all grade 1-5 adverse events |
Countries
United Kingdom
Outcome results
None listed