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

NCT ID: NCT01040832

Last Updated: 2017-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab plus EMD 1201081

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: 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.

EMD 1201081

Intervention Type: 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.

Cetuximab monotherapy

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: 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.

Interventions

Cetuximab

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.

Intervention Type: DRUG

EMD 1201081

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 Type: DRUG

Other Intervention Names

Erbitux®; IMO-2055

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMD Serono

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip Breitfeld, MD

Role: STUDY_DIRECTOR

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

Locations

University of Colorado Cancer Center

Aurora, Colorado, United States

University of Kentucky, Markey Cancer Center

Lexington, Kentucky, United States

MGH Massachusetts General Hospital

Boston, Massachusetts, United States

Montefiore Medical Center Oncology

The Bronx, New York, United States

Research Site

Brussels, , Belgium

UZ Gent

Ghent, , Belgium

Research Site

Wilrijk, , Belgium

Cliniques Universitaires Mont-Godinne

Yvoir, , Belgium

Research Site

Brno, , Czechia

Research Site

Kladno, , Czechia

Research Site

Pardubice, , Czechia

Ustav radiacni onkologie Fakultni nemacnice Na Bulovce

Prague, , Czechia

Research Site

Montpellier, , France

Research Site

Villejuif, , France

Research Site

Győr, , Hungary

Research Site

Kecskemét, , Hungary

Research Site

Miskolc, , Hungary

Research Site

Nyiregyahaza, , Hungary

Szegedi Tudomayegyetem Altalanos Orvostudomanyi Kar Onkoterapias Klinika

Szeged, , Hungary

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, , Hungary

Zala Megyei Kohaz Kulsokorhaz Onkologia Osztaly

Zalaegerszeg, , Hungary

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

Lublin, , Poland

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

Olsztyn, , Poland

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

Warsaw, , Poland

Onkologicky ustav Sv. Alzbety

Bratislava, , Slovakia

Nemocnice s poliklinikou Zilina

Žilina, , Slovakia

Velindre Cancer Centre

Cardiff, , United Kingdom

Research Site

Conventry, , United Kingdom

MHCW

Coventry, , United Kingdom

St. James' University Hospital

Leeds, , United Kingdom

Research Site

London, , United Kingdom

The Christie NHS FT

Manchester, , United Kingdom

Research Site

Newcastle upon Tyne, , United Kingdom

Weston Park Hospital

Sheffield, , United Kingdom

Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

Countries

United States; Belgium; Czechia; France; Hungary; Poland; Slovakia; United Kingdom

References

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.

Reference Type: RESULT

PMID: 24894651 (View on PubMed)

Related Links

http://www.cancer.gov/

Related Info

Other Identifiers

EMR 200068-006

Identifier Type: -

Identifier Source: org_study_id