Description:
The study will a be a biologically enriched, prospectively stratified phase II trial in RAS
wild type metastatic colorectal cancer patients progressing after first-line treatment with
oxaliplatin, fluoropyrimidines and an anti-EGFR monoclonal antibody.
All patients will receive aflibercept in combination with FOLFIRI according to the Italian
label.
Title
- Brief Title: Folfiri/aflIbercept in Metastatic coloreCTal Cancer patIents With RAS Validated Wild typE Status
- Official Title: seconD-line Folfiri/aflIbercept in proSpecTIvely Stratified, Anti-EGFR resistaNt, Metastatic coloreCTal Cancer patIents With RAS Validated Wild typE Status
Clinical Trial IDs
- ORG STUDY ID:
2017-002219-33
- NCT ID:
NCT04252456
Conditions
- Advanced Colorectal Cancer
Purpose
The study will a be a biologically enriched, prospectively stratified phase II trial in RAS
wild type metastatic colorectal cancer patients progressing after first-line treatment with
oxaliplatin, fluoropyrimidines and an anti-EGFR monoclonal antibody.
All patients will receive aflibercept in combination with FOLFIRI according to the Italian
label.
Detailed Description
The study will a be a biologically enriched, prospectively stratified phase II trial in RAS
wild type metastatic colorectal cancer patients progressing after first-line treatment with
oxaliplatin, fluoropyrimidines and an anti-EGFR monoclonal antibody. Eligible patients will
be prospectively allocated to either of two groups according to VEGFR2 levels (ELISA-based
technique, pg/ml) at study entry.
Others angiogenetic factors levels concentration before and during treatment. VEGF, PlGF,
HGF, VEGFR1, IL8, IL1a, T-cad, VEGFR3, SAP, VDBP, neuropilin1, CRP, endoglin plasma
concentrations will be evaluated before each cycle according to an ELISA-based technique All
patients will undergo a blood test for retrieving circulating tumor DNA (Liquid Biopsy) at
selected time-points before and during treatment for determining whether the status of
selected tumor biomarkers evolve during tumor progression by comparing different ctDNA
samples.
All patients will receive aflibercept in combination with FOLFIRI according to the Italian
label.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| standard chemotherapy for advanced colorectal cancer | Other | All patients will receive aflibercept in combination with FOLFIRI according to the Italian label. | |
Eligibility Criteria
Inclusion Criteria:
- • Histological confirmation of colorectal cancer
- Confirmed RAS wild type patient treated with an oxaliplatin-anti EGFR treatment
in 1st line
- At least one lesion measurable with CT or MRI scan
- Radiologically documented progression while on or after discontinuation of
treatment with FOLFOX in combination with an anti-EGFR monoclonal antibody
(either cetuximab or panitumumab)
- Radiologically documented progressing disease after FOLFOX in combination with an
anti-EGFR monoclonal antibody (either cetuximab or panitumumab)
- Life expectancy plus 3 months
- Netrophils count ³ 1.5 x 109/L
- Platelets count ³ 100 x 109/L
- Hemoglobin ³ 9 g/dL
- Creatinine £ 1.5 mg/dL, Proteinuria <2+ (dipstick urinalysis) or
≤1g/24hour.Bilirubin £ 1.5 x ULN
- AST and ALT £ 2.5 x ULN (< 5 ULN in case of liver metastases)
- Informed written consent
- ECOG Performance Status < 2
- Age plus18 yrs
- Regular follow-up feasible.
- For female patients of childbearing potential, negative serum pregnancy test
within 1 week (7 days) prior of starting study treatment,
- Female patients must commit to using reliable and appropriate methods of
contraception until at least six months after the end of study treatment
Exclusion Criteria:
- • Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular
targeted therapy, immunotherapy),
- Treatment with any other investigational medicinal product within 28 days prior
to First Study treatment.
- Other serious and uncontrolled non-malignant disease,
- History or evidence upon physical examination of CNS metastasis unless adequately
treated
- Gilbert's syndrome
- Intolerance to atropine sulfate or loperamide
- Known dihydropyrimidine dehydrogenase deficiency
- Treatment with CYP3A4 inducers unless discontinued > 7 days prior to First Study
treatment.
- Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal
bleeding (unless due to resected tumor), treatment resistant peptic ulcer
disease, erosive esophagitis or gastritis, infectious or inflammatory bowel
disease, or diverticulitis.
- Other concomitant or previous malignancy, except: i/ adequately treated in-situ
carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the
skin, iii/ cancer in complete remission for >5 years,
- Major surgery or traumatic injury within the last 28 days or until the surgical
wound is fully healed whichever came later
- Pregnant or breastfeeding women,
- Patients with known allergy to any excipient to study drugs,
- Bowel obstruction.
- Uncontrolled infections
- Known drugs or alcohol abuse
- History of severe cardiovascular disease within 6 months prior to First Study
treatment Uncontrollable hypertension, when treated with three or more drugs.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall survival (OS) according to VEGFR2 levels, evaluating the difference in terms of median OS among patients with high VEGFR2 activity and patients with low VEGFR2 activity |
| Time Frame: | From date of randomization until the date of death from any cause, whichever came first, assessed up to 3 years |
| Safety Issue: | |
| Description: | Overall survival time is defined as the time from inclusion to the date of death. If subject has not died, survival will be censored on the last date the subject was known to be alive (last date of follow-up) |
Secondary Outcome Measures
| Measure: | Progression free survival (PFS) defined as the interval between the start of Aflibercept-FOLFIRI therapy to tumor progression or death or last follow up visit if not progressed |
| Time Frame: | time from the start of treatment untill the date of first documented progression or death from any cause, whichever came first, assessed up to 3 years |
| Safety Issue: | |
| Description: | PFS time will defined as the time of inclusion until the date of first observed disease progression or death due to any cause, if death occurs before progression is documented |
| Measure: | Response rate (RR) defined according to the Response Evaluation Criteria in Solid Tumours (RECIST), v. 1.1 |
| Time Frame: | Response of treatment is evaluated according to the RECIST criteria at the end of chemotherapyassessed up to 24 weeks |
| Safety Issue: | |
| Description: | All patients must be considered in response analysis, including those who discontinue treatment or who die for any reason prior to respnse evaluation |
| Measure: | Toxicity Profile defined according to the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03 |
| Time Frame: | every 4 cycles of chemotherapy (each cycle is 15 days), up to 16 weeks |
| Safety Issue: | |
| Description: | Treatment-emergent adverse events, drug-related adverse events and safety laboratory parameters will be analysed by CTCAE grade |
| Measure: | Angiogenetic factors levels concentration before and during treatment. |
| Time Frame: | evaluated before treatment and before each cycle (each cycle is 15 days) according to an ELISA-based technique, through completion, an overage of 1 year |
| Safety Issue: | |
| Description: | Angiogenetic factors levels concentration (VEGF, PlGF, HGF, VEGF-R, IL8, IL1a, T-cad, VEGFR3, SAP, VDBP, neuropilin1, CRP, endoglin plasma concentrations) |
Details
| Phase: | N/A |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente |
Last Updated
February 5, 2020
