Elderly Metastatic Colorectal Cancer Patients
Conditions
Brief summary
* Few data are available about the treatment of metastatic colorectal cancer (mCRC) elderly patients with anti-EGFR agents in combination with chemotherapy. Up today, most of the available data are from retrospective/post-hoc analyses, making them difficult to translate to everyday clinical practice. * FOLFOX plus panitumumab is a standard first-line therapy option for RAS wild-type untreated mCRC patients. Slight adjustments in chemo-dosage are commonly applied in routinary practice to elderly patients, but those modified schedules have never been prospectively tested. * In elderly patients, a reasonable upfront treatment is a fluoropyrimidine-based monotherapy plus bevacizumab, irrespectively of the molecular status of RAS. * BRAF mutation is a strong negative prognostic factor associated to advanced age, poor performance status (PS), extended and aggressive disease and is associated to a lack of benefit from anti-EGFR moAb. * Clinical definition of elderly (over 70 years old) CRC patients that may deserve a more or less intensive combination therapy is still debated. The cut-off of 75 years old combined with ECOG PS assessment is a reasonable approach for clearly defining candidates to different approaches31. * Several geriatric screening tools have been used to identify patients with a geriatric profile potentially predicting for overall survival and risk of toxicity. The G8 screening tool has been validated in cancer patients showing the strongest prognostic value for overall survival; the CRASH score is able to stratify patients according an estimated risk of treatment-related toxicities. On the basis of these considerations, the investigators designed the present randomized phase II trial of first-line therapy panitumumab in combination with simplified FOLFOX or with 5-fluorouracil, in previously untreated elderly patients with RAS and BRAF wild-type unresectable mCRC.
Interventions
Sponsors
Gruppo Oncologico del Nord-Ovest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent to study procedures and to molecular analyses. * Histologically proven diagnosis of colorectal cancer. * Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease. * At least one measurable lesion according to RECIST1.1 criteria. * Availability of a tumoral sample (primary and/or metastatic sites). * Age ≥ 70 years. * ECOG PS 1 or 2 for patients aged 70 to 75 years; ECOG PS 0 or 1 for patients aged \> 75 years. * Life expectancy of at least 12 weeks. * Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse. * RAS and BRAF status wild-type of primary colorectal cancer or related metastasis, centrally assessed. * Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl. * Total bilirubin ≤ 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or \<5 x UNL in case of liver metastases) alkaline phosphatase ≤ 2.5 x UNL (or \<5 x UNL in case of liver metastases). * Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL. * Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception). * Geriatric assessment by means of G8 screening tool and CRASH score. * Will and ability to comply with the protocol.
Exclusion criteria
* Previous treatment for metastatic disease. * Radiotherapy to any site within 4 weeks before the study. * Previous adjuvant oxaliplatin-containing chemotherapy. * Previous treatment with EGFR inhibitors. * Untreated brain metastases or spinal cord compression or primary brain tumors. * History or evidence upon physical examination of CNS disease unless adequately treated. * Symptomatic peripheral neuropathy \> 1 grade NCIC-CTG criteria. * Creatinine clearance \< 50 mL/min or serum creatinine \>1.5 x UNL. * Clinical signs of malnutrition. * Neutrophils \<1.5 x 109/L, Platelets \<100 x 109/L, Hgb \<9 g/dl. * Diagnosis of interstitial pneumonitis or pulmonary fibrosis. * Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration. * Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication. * Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer) * Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ. * Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication. * Definite contraindications for the use of corticosteroids and antihistamines as premedication. * Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs. * Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies. * Sexually active males unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS). PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. | Up to 28 months | July 2016 - November 2018 |
Countries
Italy
Outcome results
None listed