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Completed

NCT Number: NCT01911598

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)

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Cliniques Universitaires St-Luc, Brussels, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

5-FU

Drug

5-FU will be administered as per schedule specified in the respective arm.

carboplatin

Drug

Carboplatin will be administered as per schedule specified in the respective arm.

Cisplatin

Drug

Cisplatin will be administered as per schedule specified in the respective arm.

MEHD7945A

Drug

MEHD7945A will be administered as per schedule specified in the respective arms.

Other names: Duligotuzumab

paclitaxel

Drug

Paclitaxel will be administered as per schedule specified in the respective arm.

Primary outcomes

  1. Percentage of Participants With DLTs

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

  2. 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

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. 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)

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 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)

  17. 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)

  18. 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)

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2017
Study completion
2017
First posted
Jul 30, 2013
Registry last updated
Jul 6, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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