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)

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01911598
• Other study ID #: GO28909
• Secondary ID: 2013-001285-42
• Status: Completed
• Phase: Phase 1
• First received: July 26, 2013
• Last updated: July 4, 2017
• Start date: September 19, 2013
• Est. completion date: June 22, 2017

Study information

• Verified date: July 2017
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 22, 2017
• Est. primary completion date: June 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• 5-FU
5-FU will be administered as per schedule specified in the respective arm.
• Carboplatin
Carboplatin will be administered as per schedule specified in the respective arm.
• Cisplatin
Cisplatin will be administered as per schedule specified in the respective arm.
• MEHD7945A
MEHD7945A will be administered as per schedule specified in the respective arms.
• Paclitaxel
Paclitaxel will be administered as per schedule specified in the respective arm.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Leuven Gasthuisberg	Leuven
United States	University of Colorado Cancer Center Department of Hematology	Aurora	Colorado
United States	Massachusetts General Hospital;Hematology/ Oncology	Boston	Massachusetts
United States	University of Chicago; Hematology/Oncology	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With DLTs		Cycle 1 Day 1 through Cycle 1 Day 21 (Cycle length = 3 weeks)
Primary	Percentage of Participants with Adverse Events		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	Area Under Concentration-Time Curve From Day 1 to 21 (AUC0-21d) of MEHD7945A		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)
Secondary	Maximum Serum Concentration (Cmax) of MEHD7945A		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)
Secondary	Minimum Serum Concentration (Cmin) of MEHD7945A		Pre-infusion (0 hour) on Day 1 of Cycles 1, 2, 3, 4, and 8 (each cycle = 3 weeks)
Secondary	Cmax of Cisplatin		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)
Secondary	Area Under Concentration-Time Curve From 0 to 6 Hours (AUC0-6h) of Cisplatin		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)
Secondary	Plasma Concentrations of 5-FU		Pre-infusion (0 hour) on Day 1 of Cycle 1; Day 2 of Cycle 1 (Cycle length = 3 weeks)
Secondary	Cmax of Carboplatin		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)
Secondary	AUC0-6h of Carboplatin		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)
Secondary	Cmax Normalized by Dose (Cmax/D) of Carboplatin		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)
Secondary	AUC0-6h Normalized by Dose (AUC0-6h/D) of Carboplatin		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)
Secondary	Cmax of Paclitaxel		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)
Secondary	Area Under Concentration-Time Curve From 0 to 24 Hours (AUC0-24h) of Paclitaxel		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)
Secondary	Plasma Half-Life (t1/2) of Paclitaxel		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)
Secondary	Percentage of Participants With Anti-Therapeutic Antibodies to MEHD7945A		Pre-dose (0 hour) on Day 1 of Cycles 1, 4, 8 (each cycle = 3 weeks) and at study completion (approximately 3 years)
Secondary	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)		From first dose of study drug until disease progression or death (up to approximately 3 years)
Secondary	Percentage of Participants With Disease Control (CR or PR or Stable Disease [SD]) as Assessed by Modified RECIST v1.1 Criteria		From first dose of study drug until disease progression or death (up to approximately 3 years)
Secondary	Duration of Objective Response (CR or PR) as Assessed by Modified RECIST v1.1 Criteria		From first occurrence of CR or PR until relapse or death (up to approximately 3 years)
Secondary	Progression-Free Survival as Assessed by Modified RECIST v1.1 Criteria		From first dose of study drug until disease progression or death (up to approximately 3 years)