E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck

Browse trials for

• Carcinoma 6,738
• Carcinoma, Squamous Cell 1,772
• Squamous Cell Carcinoma of Head and Neck 1,680

Keywords

• Cancer
• head and neck
• squamous cell carcinoma of the head and neck
• phase 1b
• phase 2

Carcinoma

6,738 studies on the registry are indexed under Carcinoma; 1,159 are open to participants now.

This study's enrollment of 95 is above the median of 45 across 5,167 interventional studies indexed under Carcinoma.

Lead sponsor

Eisai Inc. is the lead sponsor of 361 studies on the registry; 8 are open to participants now.

Of its 81 completed or terminated interventional studies of FDA-regulated products, 54 (67%) have results posted.

Study arms

• Active comparator
  Active Comparator; Phase 1b: Cohort 1,2,and 3

  Phase 1b: Cohort 1; 200 mg E7050 + 250 mg/m2 cetuximab Cohort 2; 300 mg E7050 + 250 mg/m2 cetuximab Cohort 3; 400mg E7050 + 250mg/m2 cetuximab Phase 2: Arm 1; MTD E7050 + 250 mg cetuximab Arm 2; 250 mg cetuximab Interventions: Drug cetuximab

  Drug: E7050 · Drug: Cetuximab

• Active comparator
  Phase 2

  Phase 2: Arm 1; MTD E7050 + 250 mg/m2 cetuximab Arm 2; 250 mg/m2 cetuximab

  Drug: E7050 · Drug: Cetuximab

Interventions

• DrugE7050

  E7050 given orally at 200, 300, or 400 mg once daily.

  Also known as: Golvatinib

• DrugCetuximab

  Cetuximab is given at an initial dose of 400 mg/m2 given as a 2-hour intravenous (IV) infusion on Day 1 of Cycle 1, followed by a dose of 250 mg/m2 given as a 1-hour IV infusion on Day 8, Day 15, and Day 22 of Cycle 1, and Day 1, Day 8, Day 15, and Day 22 of each subsequent cycle.

Primary outcomes

1. Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)

   DLT:adverse events graded as NCI CTCAEv4.0 occurring less than or equal to(\<=)28 days after treatment.Events as: Non-hematological: 1)Grade greater than or equal to(\>=)3 peripheral neuropathy; 2)Grade 3 fatigue or 2 point decline in eastern cooperative oncology group performance status that persisted for greater than(\>)7 days; 3)Grade \>=3 nausea,vomiting despite optimal antiemetic treatment; 4)Any nonhematologic toxicity of Grade \>=3, with exceptions as alopecia,single laboratory values out of normal range,hypersensitivity reaction. Hematological 1)Grade 4 neutropenia lasting \>7 days; 2)Febrile neutropenia as fever \>=38.5 degree celsius with absolute neutrophil count less than(\<)1.0\*10\^9 per liter(/L); 3)Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4)Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1)Study drug related death; 2)Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria.

   Time frame: Cycle 1 (Cycle length is equal to [=] 28 days)

2. Phase 1b: Plasma Concentration of Golvatinib When Given in Combination With Cetuximab

   Time frame: Cycle 1: 0-48 hours post-dose (Each cycle=28 days)

3. Phase 2: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs)

   TEAEs are defined as an adverse event that has an onset date, or a worsening in severity from baseline (pre-golvatinib), on or after the first dose of golvatinib. The severity was graded according to CTCAE v4.0. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event.

   Time frame: Up to 5 years 11 months

4. Phase 2: Number of Participants With Markedly Abnormal Vital Sign Values

   Time frame: Up to 4 years 4 months

5. Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings

   Physical examination was performed and included evaluation of 1) General appearance, 2) Head; Eyes; Ears; Nose; Throat (HEENT), 3) Neck, 4) Heart, 5) Chest (Including Lungs), 6) Abdomen, 7) Extremities, 8) Skin, 9) Lymph Nodes, and 10) neurological status. Here, number of participants with markedly abnormal physical examinations were reported.

   Time frame: Up to 4 years 4 months

6. Phase 2: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values

   Time frame: Up to 4 years 4 months

Secondary outcomes

1. Phase 2: Progression-free Survival (PFS)

   PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on response evaluation criteria in solid tumor (RECIST) v1.1. PD is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.

   Time frame: From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 4 years 4 months)

2. Phase 2: Percentage of Participants With PFS at Week 12

   PFS rate at week 12 is defined as the percentage of participants who were still alive without disease progression at 12 weeks from the date of randomization. PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS rate was estimated and analyzed using Kaplan Meier method.

   Time frame: At Week 12

3. Phase 2: Time to Progression (TTP)

   TTP is defined as the time from the date of randomization until the date of PD based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. TTP was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.

   Time frame: From the date of randomization until the date of PD (Up to approximately 4 years 4 months)

4. Phase 2: Overall Survival (OS)

   OS is defined as the time from the date of randomization until the date of death. OS was analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.

   Time frame: From the date of randomization until the date of death (Up to approximately 4 years 4 months)

5. Phase 2: Percentage of Participants With Overall Response

   Overall response rate is defined as percentage of participants with complete response (CR) or partial response (PR) based on RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As planned, data for this endpoint was analyzed and collected till primary completion date.

   Time frame: From the date of randomization until CR or PR (Up to approximately 4 years 4 months)

Baseline characteristics