Description:
This is a Phase 1b/2a study investigating the safety and efficacy of Sym004, an investigational medicinal product (IMP), in combination with FOLFIRI (chemotherapy) when administered every second week (Q2W).
This is a Phase 1b/2a study investigating the safety and efficacy of Sym004, an investigational medicinal product (IMP), in combination with FOLFIRI (chemotherapy) when administered every second week (Q2W).
Terminated
Phase 1/Phase 2
NCT ID: NCT02568046
ORG ID: Sym004-09
Metastatic Colorectal Cancer
Drug | Synonyms | Arms |
---|---|---|
Sym004 | Sym004 + FOLFIRI | |
Irinotecan | Sym004 + FOLFIRI | |
Folinic Acid | Sym004 + FOLFIRI | |
Fluorouracil | 5-Fluorouracil (5-FU) | Sym004 + FOLFIRI |
This is a phase 1b/2a study investigating the safety and effect of Sym004 in combination
with FOLFIRI (chemotherapy) when administered every second week.
The phase 1b (dose-escalation) portion of the trial is expected to begin Q1 2016. Patients
will be sequentially enrolled to dose-escalation cohorts until establishment of the Maximum
Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Sym004 in combination with
FOLFIRI.
The phase 2a (dose-expansion) portion of the trial is expected to begin after establishing
the RP2D.
Name | Type | Description | Interventions |
---|---|---|---|
Sym004 + FOLFIRI | Experimental | Phase 1b, dose-escalation: Dose Level 1: Sym004 12 mg/kg + FOLFIRI (Q2W) Dose Level 2: Sym004 15 mg/kg + FOLFIRI (Q2W) Dose Level 3: Sym004 18 mg/kg + FOLFIRI (Q2W) Phase 2a, dose-expansion: Receiving Sym004 in the RP2D in combination with FOLFIRI FOLFIRI regimen consists of: Irinotecan 180 mg/m2 iv, infused over 60-90 minutes, concurrently with Folinic Acid (FA) 400 mg/m2 iv, infused over 120 minutes, followed by 5-Fluorouracil (5-FU) 400 mg/m2 iv bolus, then 2400 mg/m2 5-FU infused over 46 hours | Sym004, Irinotecan, Folinic Acid, Fluorouracil |
Main inclusion Criteria:
1. Male or female, at least 18 years of age at the time of informed consent
2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
3. Histologically or cytologically confirmed, locally advanced or metastatic colorectal
cancer (CRC) that is documented to be without Kirsten rat sarcoma (KRAS) or
Neuroblastoma rat sarcoma (NRAS) gene mutations (i.e. tumors must express the KRAS
and NRAS wild type (WT), exon 2, 3 and 4).
4. Failed* treatment for locally advanced or metastatic disease with first-line
combination therapy of oxaliplatin and a fluoropyrimidine, with or without
bevacizumab, during treatment or < 3 months after the last dose of first-line therapy
and within < 3 months of C1/D1.
Patients who discontinued first-line therapy due to toxicity may be enrolled provided
progression occurred < 6 months after the last dose of the first-line therapy
regimen.
or Failed* adjuvant therapy with combination therapy of oxaliplatin and a
fluoropyrimidine during treatment or within < 6 months after the last dose of
oxaliplatin and within < 6 months of C1/D1.
- Failure is defined as radiologic progression
5. Eligible for FOLFIRI
6. Measurable disease according to RECIST v1.1
Main exclusion Criteria:
1. Prior therapy with anti-EGFR antibodies, anti-EGFR small molecule inhibitors or
irinotecan (CPT-11)
2. Any antineoplastic agent (standard or investigational) within 4 weeks prior to C1/D1
3. Significant gastrointestinal abnormalities
4. Patients with a significant cardiovascular disease or condition
5. Abnormal hematologic, renal or hepatic function
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Phase 1b: Dose-Limiting Toxicities (DLT) observed during Cycle 1 of Sym004 administration in combination with FOLFIRI.
Phase 2a: Confirmed objective antitumor response.
Number of participants with treatment-related adverse events (AEs) as assessed by NCI-CTCAE v4.03
Dose-normalized area under the concentration-time curve from End of Infusion (EOI) to 336 hours (AUCNorm, 0-336h)
Preliminary evaluation of the antineoplastic effect of Sym004 plus FOLFIRI as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Area under the concentration-time curve from EOI to 336 hours (AUC0-336h)
Maximum concentration (Cmax)
Time to reach maximum concentration (Tmax)
Trough concentration (Ctrough)
Elimination half-life (T)
Clearance (CL)
Volume of distribution (V)
Urine and peripheral blood collection for assessment of biomarkers related to the EGFR pathway
Other potential biomarkers to be determined (i.e. genes, gene transcripts and proteins of the receptor tyrosine kinases (RTKs))
Metastatic Colorectal Cancer