EMD 1201081 in Combination With Cetuximab in Second-Line Cetuximab-Naïve Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

NCT01040832 | Completed Phase 2 Results DMC

• 1 other identifier: EMR 200068-006
• Study Type: interventional
• Target: 107
• Locations: 8 countries
• Sites: 35

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.

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

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Time: Independent Read Assessments

  The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants without event were censored on the date of last tumor assessment.

  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 (4)

• Percentage of Participants With Objective Response: Independent Read Assessments

  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)

• Percentage of Participants With Disease Control: Independent Read Assessments

  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)

• Overall Survival (OS) Time

  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)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

  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)

Study Arms (2)

Cetuximab plus EMD 1201081

EXPERIMENTAL

Drug: Cetuximab; Drug: EMD 1201081

Cetuximab monotherapy

ACTIVE COMPARATOR

Drug: Cetuximab

Interventions

Cetuximab DRUG

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.

Also known as: Erbitux®

Cetuximab monotherapy; Cetuximab plus EMD 1201081

EMD 1201081 DRUG

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.

Also known as: IMO-2055

Cetuximab plus EMD 1201081

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (35)

University of Colorado Cancer Center

Aurora, Colorado, United States

Location

University of Kentucky, Markey Cancer Center

Lexington, Kentucky, United States

Location

MGH Massachusetts General Hospital

Boston, Massachusetts, United States

Location

Montefiore Medical Center Oncology

The Bronx, New York, United States

Location

Research Site

Brussels, Belgium

Location

UZ Gent

Ghent, Belgium

Location

Research Site

Wilrijk, Belgium

Location

Cliniques Universitaires Mont-Godinne

Yvoir, Belgium

Location

Research Site

Brno, Czechia

Location

Research Site

Kladno, Czechia

Location

Research Site

Pardubice, Czechia

Location

Ustav radiacni onkologie Fakultni nemacnice Na Bulovce

Prague, Czechia

Location

Research Site

Montpellier, France

Location

Research Site

Villejuif, France

Location

Research Site

Győr, Hungary

Location

Research Site

Kecskemét, Hungary

Location

Research Site

Miskolc, Hungary

Location

Research Site

Nyiregyahaza, Hungary

Location

Szegedi Tudomayegyetem Altalanos Orvostudomanyi Kar Onkoterapias Klinika

Szeged, Hungary

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, Hungary

Location

Zala Megyei Kohaz Kulsokorhaz Onkologia Osztaly

Zalaegerszeg, Hungary

Location

SPZOZ Centrum Onkologi Liemi Lubelskiej, II Odzial Radioterapiii z pododdzialem Chemioterpii

Lublin, Poland

Location

Zaklad Opleki Zdrowotnej MSWIA z Warminsko-Mazurskim Centrum Onkologil, Oddziat Chemioterapli

Olsztyn, Poland

Location

Centrum Onkologi - Instytut im. Marii Sklodowskiej-Curie, Klinika Nowotworow Glowy i Szyi (NCI)

Warsaw, Poland

Location

Onkologicky ustav Sv. Alzbety

Bratislava, Slovakia

Location

Nemocnice s poliklinikou Zilina

Žilina, Slovakia

Location

Velindre Cancer Centre

Cardiff, United Kingdom

Location

Research Site

Conventry, United Kingdom

Location

MHCW

Coventry, United Kingdom

Location

St. James' University Hospital

Leeds, United Kingdom

Location

Research Site

London, United Kingdom

Location

The Christie NHS FT

Manchester, United Kingdom

Location

Research Site

Newcastle upon Tyne, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24894651 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Head and Neck Neoplasms; Recurrence

Interventions

Cetuximab; IMO-2055

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Few of the secondary outcome measures were planned and later removed due to Sponsor's decision to discontinue development of EMD 1201081. Overall survival data was analyzed only for participants who received EMD 1201081 plus cetuximab.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Philip Breitfeld, MD

  EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2009
• First Posted: December 30, 2009
• Study Start: December 1, 2009
• Primary Completion: January 1, 2012
• Last Updated: January 30, 2017
• Results First Posted: July 29, 2014

Record last verified: 2014-07

Locations

FR (2); SL (2); BE (4); CZ (4); US (4); HU (7); PL (3); GB (9)