A Study of MEHD7945A in Combination With Cisplatin and 5-Fluorouracil (5-FU) or Paclitaxel and Carboplatin in Participants With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)

Phase 1CompletedNCT01911598

Genentech, Inc.24 enrolled

Overview

This open-label, multicenter study will evaluate the safety, tolerability, and pharmacokinetics of MEHD7945A in combination with chemotherapy (either cisplatin plus 5-FU or carboplatin plus paclitaxel) in participants with previously untreated R/M SCCHN. There are two stages for each arm in this study: a Dose-limiting Toxicity (DLT)-evaluation stage (Stage I) and a cohort-expansion stage (Stage II). In Stage I, DLTs will be assessed during a DLT Assessment Window of 21 days (i.e., Cycle 1 Day 1 through Cycle 1 Day 21) for both arms. In Stage II, participants will be enrolled to further characterize the safety, pharmacokinetics, and anti-tumor activity of MEHD7945A in combination with cisplatin + 5-FU or carboplatin + paclitaxel at the identified recommended Phase II dose.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Head and Neck Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirmed R/M SCCHN of mucosal origin (e.g., oral cavity, oropharynx, hypopharynx, larynx) that is not amenable to further curative local therapy (e.g., surgery, radiation including re-irradiation) (1L R/M) * Participants with unknown primary SCCHN presumed to be of head and neck mucosal origin are eligible if they meet all other entry criteria * For participants who present with de novo metastatic disease, no prior systemic chemotherapy is allowed * For participants with recurrent SCCHN, prior systemic therapy is allowed if it was given as part of induction or definitive therapy. If participants have received prior combined chemo-radiation therapy, they must be off therapy for at least 3 months * Consent to provide archival tumor tissue for biomarker testing * Life expectancy greater than or equal to (\>/=) 12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Disease that is measurable per modified RECIST v1.1 * Adequate bone marrow and organ function Exclusion Criteria: * Nasopharyngeal cancer * Prior treatment with an investigational or approved agent for the purpose of inhibiting human epidermal growth factor receptor (HER) family members. This includes, but is not limited to, cetuximab, panitumumab, erlotinib, gefitinib, and lapatinib * Prior treatment with an epidermal growth factor receptor (EGFR) inhibitor is allowed if it was administered as part of definitive therapy for locally advanced disease and completed/terminated \>/= 3 months before study enrollment * Major surgical procedure within 4 weeks prior to Day 1 * Leptomeningeal disease as the only manifestation of the current malignancy * Active infection requiring antibiotics * Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs (NSAIDs) * Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy * Current severe, uncontrolled systemic disease * History of cardiac heart failure of New York Heart Association Class II or greater or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation and paroxysmal supraventricular tachycardia) * History of myocardial infarction within 6 months prior to Cycle 1, Day 1, or history of unstable angina * Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis * History of bleeding diathesis or coagulopathy other than that due to anticoagulation therapy * Clinically significant gastrointestinal (GI) bleeding within 6 months prior to Cycle 1, Day 1 * History of interstitial lung disease (ILD) * History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy * Known human immunodeficiency virus (HIV) infection * Untreated/active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) * Pregnant or lactating women * Malignancies other than SCCHN within 5 years prior to enrollment, with the exception of adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix or skin (e.g., melanoma in situ) or indolent prostate cancer

Outcomes

Primary Outcomes

Percentage of Participants With DLTs

Time frame: Cycle 1 Day 1 through Cycle 1 Day 21 (Cycle length = 3 weeks)

Percentage of Participants with Adverse Events

Time frame: From Baseline until 45 days after last dose of study drug or until initiation of another anti-cancer therapy, withdrawal or lost to follow-up, whichever occurs first (up to approximately 3 years)

Secondary Outcomes

Area Under Concentration-Time Curve From Day 1 to 21 (AUC0-21d) of MEHD7945A

Time frame: Pre-infusion (0 hour), 30 minutes post-infusion (infusion duration=90 minutes) on Day 1 of Cycles 1, 2, 3, 4, 8; 4 hours post-infusion on Day 1 of Cycle 1; Days 2, 4, 8, 15 of Cycle 1 (each cycle = 3 weeks)

Maximum Serum Concentration (Cmax) of MEHD7945A

Time frame: 30 minutes and 4 hours post-infusion (infusion duration=90 minutes) on Day 1 of Cycle 1; 30 min post-infusion on Day 1 of Cycles 2, 3, 4, and 8 (each cycle = 3 weeks)

Minimum Serum Concentration (Cmin) of MEHD7945A

Time frame: Pre-infusion (0 hour) on Day 1 of Cycles 1, 2, 3, 4, and 8 (each cycle = 3 weeks)

Cmax of Cisplatin

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 1-2 hours) on Day 1 of Cycle 1 (Cycle length = 3 weeks)

Area Under Concentration-Time Curve From 0 to 6 Hours (AUC0-6h) of Cisplatin

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 1-2 hours) on Day 1 of Cycle 1 (Cycle length = 3 weeks)

Plasma Concentrations of 5-FU

Time frame: Pre-infusion (0 hour) on Day 1 of Cycle 1; Day 2 of Cycle 1 (Cycle length = 3 weeks)

Cmax of Carboplatin

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 15-30 minutes) on Day 1 of Cycle 1 (Cycle length = 3 weeks)

AUC0-6h of Carboplatin

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 15-30 minutes) on Day 1 of Cycle 1 (Cycle length = 3 weeks)

Cmax Normalized by Dose (Cmax/D) of Carboplatin

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 15-30 minutes) on Day 1 of Cycle 1 (Cycle length = 3 weeks)

AUC0-6h Normalized by Dose (AUC0-6h/D) of Carboplatin

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 2, 4, 6 hours post-infusion (infusion duration = 15-30 minutes) on Day 1 of Cycle 1 (Cycle length = 3 weeks)

Cmax of Paclitaxel

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 3, 5 hours post-infusion (infusion duration = 3 hours) on Day 1 of Cycle 1, Day 2 of Cycle 1 (Cycle length = 3 weeks)

Area Under Concentration-Time Curve From 0 to 24 Hours (AUC0-24h) of Paclitaxel

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 3, 5 hours post-infusion (infusion duration = 3 hours) on Day 1 of Cycle 1, Day 2 of Cycle 1 (Cycle length = 3 weeks)

Plasma Half-Life (t1/2) of Paclitaxel

Time frame: Pre-infusion (0 hour), 0 to 5 minutes and 1, 3, 5 hours post-infusion (infusion duration = 3 hours) on Day 1 of Cycle 1, Day 2 of Cycle 1 (Cycle length = 3 weeks)

Percentage of Participants With Anti-Therapeutic Antibodies to MEHD7945A

Time frame: Pre-dose (0 hour) on Day 1 of Cycles 1, 4, 8 (each cycle = 3 weeks) and at study completion (approximately 3 years)

Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Time frame: From first dose of study drug until disease progression or death (up to approximately 3 years)

Percentage of Participants With Disease Control (CR or PR or Stable Disease [SD]) as Assessed by Modified RECIST v1.1 Criteria

Time frame: From first dose of study drug until disease progression or death (up to approximately 3 years)

Duration of Objective Response (CR or PR) as Assessed by Modified RECIST v1.1 Criteria

Time frame: From first occurrence of CR or PR until relapse or death (up to approximately 3 years)

Progression-Free Survival as Assessed by Modified RECIST v1.1 Criteria

Time frame: From first dose of study drug until disease progression or death (up to approximately 3 years)

A Study of MEHD7945A in Combination With Cisplatin and 5-Fluorouracil (5-FU) or Paclitaxel and Carboplatin in Participants With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)

Overview

Conditions

Interventions

Eligibility

Locations (6)

Outcomes

Primary Outcomes

Secondary Outcomes