Clinical trial NCT01040832: EMD 1201081 in Combination With Cetuximab in Second-Line Cetuximab-Naïve Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Official title: A Phase II, Open-label, 1:1 Randomized, Controlled Trial Exploring the Efficacy of EMD 1201081 in Combination With Cetuximab in Second-Line Cetuximab-Naïve Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck Cancer
Keywords: Head and Neck Cancer
Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer
Cetuximab
EMD 1201081
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2009-12-30
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Progression-free Survival (PFS) Time: Independent Read Assessments
timeFrame: Every 6 weeks until disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date (11 Jan 2012)
Secondary outcomes:
measure: Percentage of Participants With Objective Response: Independent Read Assessments
timeFrame: Every 6 weeks until disease progression, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date (11 Jan 2012)
measure: Percentage of Participants With Disease Control: Independent Read Assessments
timeFrame: Every 6 weeks until disease progression, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date (11 Jan 2012)
measure: Overall Survival (OS) Time
timeFrame: Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date, (11 Jan 2012)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Time from first dose up to Day 42 to 49 after last dose of trial treatment, reported between day of first participant randomized, that is, 17 Dec 2009 until cut-off date, (11 Jan 2012)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Lexington
country: United States
facility: University of Kentucky, Markey Cancer Center
state: Kentucky
city: Boston
country: United States
facility: MGH Massachusetts General Hospital
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center Oncology
state: New York
city: Brussels
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: UZ Gent
city: Wilrijk
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Cliniques Universitaires Mont-Godinne
city: Brno
country: Czech Republic
facility: Research Site
city: Kladno
country: Czech Republic
facility: Research Site
city: Pardubice
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Ustav radiacni onkologie Fakultni nemacnice Na Bulovce
city: Montpellier
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Győr
country: Hungary
facility: Research Site
city: Kecskemét
country: Hungary
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Nyiregyahaza
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Szegedi Tudomayegyetem Altalanos Orvostudomanyi Kar Onkoterapias Klinika
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Kohaz Kulsokorhaz Onkologia Osztaly
city: Lublin
country: Poland
facility: SPZOZ Centrum Onkologi Liemi Lubelskiej, II Odzial Radioterapiii z pododdzialem Chemioterpii
city: Olsztyn
country: Poland
facility: Zaklad Opleki Zdrowotnej MSWIA z Warminsko-Mazurskim Centrum Onkologil, Oddziat Chemioterapli
city: Warszawa
country: Poland
facility: Centrum Onkologi - Instytut im. Marii Sklodowskiej-Curie, Klinika Nowotworow Glowy i Szyi (NCI)
city: Bratislava
country: Slovakia
facility: Onkologicky ustav Sv. Alzbety
city: Zilina
country: Slovakia
facility: Nemocnice s poliklinikou Zilina
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Conventry
country: United Kingdom
facility: Research Site
city: Coventry
country: United Kingdom
facility: MHCW
city: Leeds
country: United Kingdom
facility: St. James' University Hospital
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: The Christie NHS FT
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
Study officials:
affiliation: EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
name: Philip Breitfeld, MD
role: STUDY_DIRECTOR
References:
citation: Ruzsa A, Sen M, Evans M, Lee LW, Hideghety K, Rottey S, Klimak P, Holeckova P, Fayette J, Csoszi T, Erfan J, Forssmann U, Goddemeier T, Bexon A, Nutting C; NA EMD 1201081 Study Group. Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naive patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Invest New Drugs. 2014 Dec;32(6):1278-84. doi: 10.1007/s10637-014-0117-2. Epub 2014 Jun 4.