Clinical Trials /

Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

NCT02568046

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).

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Sym004</span> in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients

Title

  • Brief Title: Sym004 in Combination With FOLFIRI in Metastatic Colorectal Cancer Patients
  • Official Title: An Open Label, Multi-Center Phase 1b/2a Trial Investigating Different Doses of Sym004 in Combination With FOLFIRI in Patients With Metastatic Colorectal Cancer Progressing After First Line Therapy
  • Clinical Trial IDs

    NCT ID: NCT02568046

    ORG ID: Sym004-09

    Trial Conditions

    Metastatic Colorectal Cancer

    Trial Interventions

    Drug Synonyms Arms
    Sym004 Sym004 + FOLFIRI
    Irinotecan Sym004 + FOLFIRI
    Folinic Acid Sym004 + FOLFIRI
    Fluorouracil 5-Fluorouracil (5-FU) Sym004 + FOLFIRI

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    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

    Eligibility Criteria

    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

    Primary Outcome Measures

    Phase 1b: Dose-Limiting Toxicities (DLT) observed during Cycle 1 of Sym004 administration in combination with FOLFIRI.

    Phase 2a: Confirmed objective antitumor response.

    Secondary Outcome Measures

    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))

    Trial Keywords

    Metastatic Colorectal Cancer