Overview

This trial is active, not recruiting.

Condition head and neck cancer
Treatments 5-fu, carboplatin, cisplatin, mehd7945a, paclitaxel
Phase phase 1
Targets EGFR, HER3
Sponsor Genentech, Inc.
Start date September 2013
End date December 2016
Trial size 24 participants
Trial identifier NCT01911598, 2013-001285-42, GO28909

Summary

This open-label, multicenter study will evaluate the safety, tolerability, and pharmacokinetics of MEHD7945A in combination with chemotherapy in patients with recurrent/metastatic squamous cell carcinoma of the head and neck. Patients will receive MEHD7945A intravenously every 3 weeks (= 1 Cycle) in combination with either cisplatin plus 5-Flourouracil (5-FU) or carboplatin plus paclitaxel (chemotherapy treatments will be administered for a maximum of 6 Cycles). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants with previously untreated R/M SCCHN will receive intravenous (IV) MEHD7945A with IV paclitaxel and IV carboplatin.
carboplatin
Carboplatin 6 AUC administered by IV infusion at 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 every 3 weeks, up to 6 cycles
mehd7945a
1650 mg by IV infusion on Day 1 every 3 weeks
paclitaxel
200 mg/m^2 IV Day 1 every 3 weeks, up to 6 cycles.
(Experimental)
Participants with previously untreated R/M SCCHN will receive IV MEHD7945A with IV cisplatin and IV 5-FU.
5-fu
1000 milligrams per meter square per day (mg/m^2/day) as a continuos IV infusion over Days 1-4 every 3 weeks, up to 6 cycles.
cisplatin
100 mg/m^2 IV Day 1 every 3 weeks, up to 6 cycles
mehd7945a
1650 mg by IV infusion on Day 1 every 3 weeks

Primary Outcomes

Measure
Percentage of Participants with Adverse Events
time frame: approximately 28 months
Percentage of Participants With Dose-Limiting Toxicities
time frame: 21 days

Secondary Outcomes

Measure
Serum Anti-Therapeutic Antibodies to MEHD7945A
time frame: Pre-dose (0 hour) on Day 1 of Cycles 1, 4, 8 and at study completion (approximately 32 months)
Percentage of Participants with Complete Response (CR) or Partial Response (PR)
time frame: approximately 24 months
Percentage of Participants with CR or PR or Stable Disease (SD)
time frame: approximately 24 months
Duration of CR or PR
time frame: approximately 24 months
Progression-Free Survival
time frame: approximately 24 months
Area Under Concentration-Time Curve (AUC) of MEHD7945A
time frame: Pre-dose (0 hour), 30 minute post-dose on Day 1 of Cycles 1, 2, 3, 4, 8; 4 hours post-dose on Day 1 of Cycle 1; Days 2, 4, 8, 15 of Cycle 1
Maximum Serum Concentration (Cmax) of MEHD7945A
time frame: Day 1 of Cycles 1, 2, 3, 4, and 8 post-dose
Minimum Serum Concentration (Cmin) of MEHD7945A
time frame: Pre-dose (0 hour) on Day 1 of Cycles 1, 2, 3, 4, and 8
Cmax of Cisplatin
time frame: Pre-dose (0 hour), 0 to 5 minute, 1, 2, 4, 6 hours post-dose on Day 1 of Cycle 1
AUC of Cisplatin
time frame: Pre-dose (0 hour), 0 to 5 minute, 1, 2, 4, 6 hours post-dose on Day 1 of Cycle 1
Plasma Concentrations of 5-Flourouracil (5-FU)
time frame: Pre-dose (0 hour) on Day 1 of Cycle 1, Day 2
Cmax of Carboplatin
time frame: Pre-dose (0 hour), 0 to 5 minute, 1, 2, 4, 6 hours post-dose on Day 1 of Cycle 1
AUC of Carboplatin
time frame: Pre-dose (0 hour), 0 to 5 minute, 1, 2, 4, 6 hours post-dose on Day 1 of Cycle 1
Cmax of Paclitaxel
time frame: Pre-dose (0 hour), 0 to 5 minute, 1, 3, 5 hours post-dose on Day 1 of Cycle 1, Day 2
AUC of Paclitaxel
time frame: Pre-dose (0 hour), 0 to 5 minute, 1, 3, 5 hours post-dose on Day 1 of Cycle 1, Day 2

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (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) - Patients with unknown primary SCCHN presumed to be of head and neck mucosal origin are eligible if they meet all other entry criteria - For patients who present with de novo metastatic disease, no prior systemic chemotherapy is allowed - For patients with recurrent SCCHN, prior systemic therapy is allowed if it was given as part of induction or definitive therapy. If patients 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 Response Evaluation Criteria in Solid Tumors (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 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 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) - Pregnancy (positive pregnancy test) or lactation - 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

Additional Information

Official title A Phase 1b Open-Label Study of the Safety and Pharmacokinetics of MEHD7945A in Combination With Either Cisplatin and 5-FU or Paclitaxel and Carboplatin in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Genentech, Inc..