EMD 1201081 in Combination With Cetuximab in Second-Line Cetuximab-Naïve Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Condition: Squamous Cell Carcinoma of the Head and Neck Cancer
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck
Intervention: Cetuximab; EMD 1201081
Intervention description: Cetuximab weekly (initial dose 400 milligram per square meter [mg/m^2] over 120 minutes followed by 250 mg/m^2 intravenous infusion over 60 minutes) will be administered in 3-week treatment cycle until disease progression. The total treatment period will be approximately 18 months.; EMD 1201081 weekly (0.32 milligram per kilogram [mg/kg] by subcutaneous injection) will be administered in 3-week treatment cycle until disease progression. Subjects who will discontinue cetuximab due to toxicity in cetuximab monotherapy, could continue to receive EMD 1201081 monotherapy until disease progression. The total treatment period will be approximately 18 months.
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 107.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Cancer; Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer; Cetuximab; EMD 1201081

Summary:

      The purpose of this study is to determine if EMD 1201081 in combination with cetuximab is
      more efficient than cetuximab alone to control the cancer.

      EMD 1201081 is an immune modulatory oligonucleotide (IMO) containing phosphorothioate
      oligodeoxynucleotide and acts as an agonist of Toll-like receptor 9 (TLR9).

      EMD 1201081 has been studied in six clinical trials in over 170 subjects either as a
      monotherapy or in combination with chemotherapeutic agents or targeted therapies. Two studies
      have been conducted in healthy volunteers. In the other five studies, subjects with advanced
      solid tumors, renal cell carcinoma, non-small cell lung cancer and colorectal cancer have
      been treated with EMD 1201081. Two studies are still ongoing. Future clinical development of
      EMD 1201081 will focus on colorectal cancer (CRC) and squamous cell cancer of the head and
      neck (SCCHN).

      In this Phase 2 study, subjects with recurrent or metastatic squamous cell cancer of the head
      and neck (R/M SCCHN), will be treated with cetuximab plus EMD 1201081 or cetuximab alone. The
      study will be conducted as a multicenter study in several European Union (EU) member states
      and the Unites States.

      EMD 1201081 in combination with cetuximab will be evaluated for antitumor activity in
      subjects by examining its effects on accepted clinical endpoints. Progression-free survival
      (PFS) will be evaluated in subjects treated with EMD 1201081 plus cetuximab compared to
      cetuximab alone in cetuximab-naïve subjects with R/M SCCHN who have progressed on a cytotoxic
      therapy.

      Cetuximab, approved in colorectal cancer and SCCHN in combination with platinum-based
      chemotherapy and SCCHN in combination with radiotherapy in the EU, will be provided as
      investigational medicinal product (IMP) in this study. Commercially available Cetuximab will
      be provided in the United States.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated written informed consent prior to any trial-specific procedure

          -  Male or female subjects age greater than or equal to (>=) 18 years with R/M SCCHN

          -  Histologically confirmed R/M SCCHN, documented in the medical record

          -  History of progressing disease on a first-line cytotoxic chemotherapy regimen for R/M
             SCCHN, such as 5-fluorouracil (FU) plus cisplatin, or taxanes. (A history of
             chemotherapy or radiotherapy for localized disease was not considered a first-line
             regimen)

          -  The subject is suited for systemic therapy in the opinion of the Investigator

          -  At least one radiographically documented lesion measurable according to response
             evaluation criteria in solid tumors (RECIST) 1.0. All target lesions are to be
             measurable (that is, the lesion must be adequately measurable in at least one
             dimension; longest diameter to be recorded as >= 2 centimeter (cm) by conventional
             techniques or >= 1 centimeter (cm) by spiral computed tomography [CT] scan). Target
             lesions are to be selected from the required protocol imaging. If the sole site of
             measurable disease is in a prior radiation field, there has to be unequivocal evidence
             of progression at >= 8 weeks since the completion of radiation or a positive biopsy

          -  Eastern cooperative oncology group performance status (ECOG PS) of 0 or 1

          -  If female, either post-menopausal, surgically sterile, or having a negative urine or
             serum pregnancy test (beta-human chorionic gonadotropin [beta-HCG]) at screening and
             practicing medically accepted contraception. If male, practicing contraception if the
             risk of conception exists. For relevant subjects, the duration of contraception should
             be 1 week prior to the start of therapy through 4 weeks after receipt of trial therapy

          -  Recovered from previous toxicities of prior cytotoxic regimen to common terminology
             criteria of adverse events (CTCAE) Grade 1 (with the exception of alopecia)

          -  Hemoglobin >= 9 gram per deciliter (g/dL) without transfusion support; no transfusion
             within 7 days prior to screening)

          -  Neutrophils >= 1.5 * 10^9 per liter

          -  Platelets >= 100 * 10^9 per liter

          -  Prothrombin time/partial thromboplastin time (PT/PTT) less than or equal to (=<) 1.5
             times the upper limit of normal (ULN) for the site, unless there is therapeutic
             anti-coagulation

          -  Serum creatinine =< 1.5 times the ULN for the site

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the ULN
             for the site

          -  Be willing and able to comply with the protocol procedures for the duration of the
             trial

        Exclusion Criteria:

          -  History of prior exposure to cetuximab or panitumumab or any other approved or
             investigational anti-epidermal growth factor receptor (EGFR) agents

          -  Undifferentiated nasopharyngeal carcinoma

          -  Chemotherapy, radiotherapy or any investigational agents within 4 weeks prior to first
             dose of study drug

          -  Major surgical or planned procedure within 30 days prior to first dose of trial
             medication (isolated biopsies are not considered major surgical procedures)

          -  Active malignancy other than SCCHN, non-metastatic basal cell or squamous cell
             carcinoma of the skin, or second primary SCCHN

          -  Impaired cardiac function (for example, left ventricular ejection fraction less than
             [<] 45 percent defined by echocardiograph or other study), history of uncontrolled
             serious arrhythmia, unstable angina pectoris, congestive heart failure (new york heart
             association [NYHA] Grade III and IV), myocardial infarction within the last 12 months
             prior to trial entry, or signs of pericardial effusion

          -  Hypertension uncontrolled by standard pharmacologic therapies

          -  History of diagnosed interstitial lung disease

          -  Subject requires systemic anti-coagulation (example, warfarin greater than [>] 10
             milligram per day [mg/day])

          -  Pregnancy or breastfeeding

          -  Legal incapacity or limited legal capacity

          -  Significant medical or psychiatric disease which makes the trial inappropriate in the
             Investigator's opinion

          -  Any brain metastasis and/or leptomeningeal disease (known or suspected)

          -  Significant pre-existing immune deficiency, such as infection of human
             immuno-deficiency virus (HIV) (documented or known)

          -  Clinically significant ongoing infection

          -  Known hypersensitivity to the trial treatments

          -  Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family
             members who suffer from such disease

          -  Other significant disease that in the Investigator's opinion would exclude the subject
             from the trial