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Sym004 in Subjects With Stage IV Non-small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT02083679
Recruitment Status : Terminated (Sponsor the return rights of the compound to the collaboration partner for further clinical development)
First Posted : March 11, 2014
Results First Posted : October 25, 2016
Last Update Posted : October 25, 2016
Sponsor:
Information provided by (Responsible Party):
EMD Serono

Brief Summary:

This is a multi-center, open-label, Phase 1b, dose escalation trial of Sym004 administered in combination with 1 of 3 platinum-doublets in subjects with Stage IV Non-Small Cell Lung Cancer (NSCLC).

The sponsor decided to discontinue the development of Sym004. Also the decision was made to discontinue the development of Sym004 in NSCLC indication. The decision to discontinue Sym004 in NSCLC was not related to any safety or efficacy findings regarding Sym004. As a result of the early discontinuation of the trial during the dose escalation part, the expansion cohort will no longer be performed hence the pre-specified secondary endpoints are not analyzed and were removed from the protocol based on protocol amendment 2 dated 31 March 2015.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Drug: Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Drug: Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-label, Dose Escalation Trial Investigating Different Doses and Schedules of Sym004 in Combination With Platinum-doublets in Subjects With Stage IV Non-small Cell Lung Cancer
Study Start Date : July 2014
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine
Sym004 will be administered as an intravenous infusion at a dose of 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject meets any of the criteria for subject withdrawal, or withdrawal from the investigational medicinal product (IMP) in combination with platinum-doublet chemotherapy regimen of cisplatin/gemcitabine (cisplatin 75 mg/m^2 on Day 1 plus gemcitabine 1250 mg/m^2 on Days 1 and 8 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).

Experimental: Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed
Sym004 will be administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject meets any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of cisplatin/pemetrexed (cisplatin 75 mg/m^2 plus pemetrexed 500 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).

Experimental: Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Drug: Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel
Sym004 will be administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject meets any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin area under the concentration-time curve (AUC) = 6 milligram per millilitre per minute [mg/mL/min] plus paclitaxel 225 mg/m^2 on Day 1 of 3-Week cycle intravenously for a maximum of 6 treatment cycles).

Experimental: Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel Drug: Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Sym004 will be administered as an intravenous infusion at a dose 6 mg/kg on Day 1 and 12 mg/kg on Day 8 of a 3-Week cycle until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject meets any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin AUC = 6 mg/mL/min plus paclitaxel 225 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).




Primary Outcome Measures :
  1. Number of Subjects With Dose Limiting Toxicities (DLTs) [ Time Frame: Day 1 to Day 21 of Cycle 1 ]
    DLT: any National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 Grade 4 hematologic or Grade 3/4 non-hematologic toxicities that occurred during DLT observation period and were considered by Investigator to be at least possibly related to trial treatment, and were confirmed by Safety Monitoring Committee (SMC), with exception of Grade 4 neutropenia for not >5 days; Grade 4 lymphocytopenia/ thrombocytopenia for not >5 days; fatigue/headache lasting < 7 days; nausea/vomiting/diarrhoea lasting not >3 days; asymptomatic Grade 3 increase in liver function tests that resolve to baseline within 7 days; Mucositis >= Grade 3 lasting < 7 days; Grade 3 hyperglycemia that resolves in < 7 days; any laboratory values >Grade 3 without any clinical correlate (resolve within 5 days); Grade 3 skin toxicities that resolve to Grade 2 within 7 days; Grade 3/4 hypomagnesemia that resolves within 5 days. Subjects with DLTs presented based on investigator and SMC decision.


Secondary Outcome Measures :
  1. Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death [ Time Frame: Day 1 up to 28 days after last dose of study drug (up to 53 weeks) ]
    An adverse event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. AEs were considered treatment emergent if they started on or after the day of first administration of the first trial treatment given (Sym004 or one of the individual Platinum-Doublet therapies) or if they worsened after receiving first dose of treatment.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female outpatients (except where inpatient stay is required for medical need at the Investigator's discretion) at least 18 years of age at the time of informed consent
  • Histologically-confirmed NSCLC Stage IV disease (according to the seventh edition of the lung cancer staging system)
  • Eligibility for platinum-based chemotherapy
  • Tumor tissue available for epidermal growth factor receptor (EGFR) expression analysis
  • Measurable disease defined as 1 or more target lesions according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
  • Life expectancy of at least 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Previous therapy for Stage IV NSCLC, or neo- or adjuvant chemotherapy or chemoradiotherapy within the previous 6 months
  • Previous investigational drug or any anticancer therapy in the 30 days (or 5 half-lives for non-cytotoxics, whichever is shorter) prior to the start of trial treatment
  • In countries where anaplastic lymphoma kinase (ALK) inhibitors are available for the treatment of NSCLC, subjects need to have been screened for ALK fusion gene rearrangements and excluded if positive, unless previously treated and progressed on an appropriate tyrosine kinase inhibitor (TKI) therapy
  • In countries where EGFR TKIs are available for the treatment of NSCLC, subjects need to have been screened for EGFR mutations and excluded if positive, unless previously treated and progressed on an appropriate TKI therapy
  • Concurrent chronic immunosuppressive or hormone anticancer therapy (except other physiologic hormone replacement)
  • Known brain metastases (unless asymptomatic and treated) or leptomeningeal metastases, including suspected leptomeningeal spread with positive cytology
  • History of any other malignancy within 5 years (except basal cell carcinoma of the skin or carcinoma in situ of the cervix)
  • Other protocol defined exclusion criteria could apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02083679


Locations
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United States, Massachusetts
Please Contact U.S. Medical Information Located in
Rockland, Massachusetts, United States
Germany
Please contact the Merck KGaA Communication Center located in
Darmstadt, Germany
Sponsors and Collaborators
EMD Serono
Investigators
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany

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Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT02083679     History of Changes
Other Study ID Numbers: EMR200637-003
2013-003995-11 ( EudraCT Number )
First Posted: March 11, 2014    Key Record Dates
Results First Posted: October 25, 2016
Last Update Posted: October 25, 2016
Last Verified: August 2016

Keywords provided by EMD Serono:
Carcinoma, Non-Small-Cell Lung
Sym004

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Gemcitabine
Carboplatin
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs