Trial Outcomes & Findings for Cetuximab With Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects (NCT NCT01012258)

Last Updated: 2015-07-09

Results Overview

Best overall (objective) response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to modified World Health Organization (WHO) criteria confirmed at a repeat assessment performed no less than 28 days after the criteria for response were first met. CR was defined as disappearance of all index lesions. PR was defined as a 50% or more decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of PD.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

70 participants

Primary outcome timeframe

Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 3 months following the 8 weeks after the end of RT visit until the end of trial (EOT) visit

Results posted on

2015-07-09

Participant Flow

A total of 70 participants were screened, out of which 4 participants were not treated and 66 participants received the study treatment.

Participant milestones

Participant milestones
Measure	Cetuximab Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval.
Overall Study STARTED	66
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	66

Reasons for withdrawal

Reasons for withdrawal
Measure	Cetuximab Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval.
Overall Study Death	14
Overall Study Lost to Follow-up	1
Overall Study Adverse Event	1
Overall Study Progressive Disease (PD)	18
Overall Study Symptomatic Deterioration	1
Overall Study Another Anti-cancer Drug Received	1
Overall Study Another Tumor Discovered	1
Overall Study Ongoing	29

Baseline Characteristics

Cetuximab With Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cetuximab n=66 Participants Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval.
Age, Continuous	55.8 years STANDARD_DEVIATION 9.5 • n=5 Participants
Age, Customized <65 years	52 participants n=5 Participants
Age, Customized >=65 years	14 participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 3 months following the 8 weeks after the end of RT visit until the end of trial (EOT) visit

Population: Intention-to-treat (ITT) population included all participants who received at least one dose of the investigational medicinal product (IMP) cetuximab or RT.

Outcome measures

Outcome measures
Measure	Cetuximab n=66 Participants Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval.
Best Overall Response (BOR)	68.2 percentage of participants Interval 55.6 to 79.1

SECONDARY outcome

Timeframe: Baseline up to disease progression or withdrawal or 12 weeks after the last radiotherapy of the last participant

Population: ITT population included all participants who received at least one dose of the IMP cetuximab or RT.

Progression-free survival was defined as the duration (in months) from first administration of trial treatment to first observation of PD (radiological or clinical, if radiological PD is not available), or death due to any cause. The PFS time of participants without observation of PD but death occurring after two or more missed consecutive tumor assessments (i.e. two-fold scheduled time interval of two consecutive tumor assessments) was censored on the date of last tumor assessment or first administration of trial treatment (whichever was later).

Outcome measures

Outcome measures
Measure	Cetuximab n=66 Participants Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval.
Progression-Free Survival (PFS)	9.4 months Interval 7.7 to 11.2

Adverse Events

Cetuximab: Treatment Emergent Phase

Serious events: 5 serious events

Other events: 64 other events

Deaths: 0 deaths

Cetuximab: Late Phase

Serious events: 14 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Responsible

Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd.

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All submissions by the PI for publication require the written permission from the sponsor. The PI commits to forward to the sponsor all documents intended for publication which contains data or results generated in connection with the study. Documents must be available at least 60 days before the planned submission date to allow for review. Any publication should follow the policy in the protocol. The PI shall not publish results derived from the study until the study has been reported in full.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cetuximab: Treatment Emergent Phase n=66 participants at risk Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. Treatment emergent phase, i.e. treatment-emergent adverse events (TEAEs, adverse events which occur or worsen on the first dosing day of trial treatment and until 60 days after the last trial treatment administration (cetuximab or radiotherapy).	Cetuximab: Late Phase n=62 participants at risk Participants received cetuximab 400 milligram/square meter (mg/m\^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m\^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. Late phase, i.e. adverse events which occur or worsen more than 60 days after the last trial treatment administration (cetuximab or radiotherapy), and before end of trial.
Blood and lymphatic system disorders Iron deficiency anemia	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Hematemesis	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
General disorders Localized edema	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
General disorders Sudden death	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Immune system disorders Drug hypersensitivity	3.0% 2/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	0.00% 0/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Lung infection	1.5% 1/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	3.2% 2/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Pneumonia	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Injury, poisoning and procedural complications Tracheal obstruction	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Metabolism and nutrition disorders Cachexia	1.5% 1/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	3.2% 2/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Esophageal carcinoma	1.5% 1/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	0.00% 0/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Paresthesia	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Asphyxia	1.5% 1/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Laryngeal edema	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Respiratory, thoracic and mediastinal disorders Pharyngeal hemorrhage	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	3.2% 2/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Vascular disorders Hemorrhage	0.00% 0/66 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.	1.6% 1/62 • Up to Day 60 after last trial treatment administration and before EOT An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.