Docetaxel, Cisplatin, and Cetuximab (TPC) in Palliative Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck (SCCHN)

• ClinicalTrials.gov Identifier: NCT01437449
• Recruitment Status: Completed
• First Posted: September 20, 2011
• Results First Posted: December 17, 2019
• Last Update Posted: December 17, 2019
• Sponsor: Stanford University
• Information provided by (Responsible Party): A. Dimitrios Colevas, Stanford University

Study Description

Brief Summary:

Docetaxel and cetuximab are FDA-approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN). Cisplatin and carboplatin, while not FDA-approved for SCCHN, have been used as standard of care in SCCHN patients in combination with other drugs. This study evaluates if weekly cisplatin and docetaxel, in combination with cetuximab, is effective in palliative treatment of patients with SCCHN. These drugs will be given intravenously weekly, repeated 3 of every 4 weeks until evidence of disease progression or unacceptable adverse events.

Condition or disease	Intervention/treatment	Phase
Head and Neck Cancer	Drug: Docetaxel; Drug: Cisplatin; Drug: Cetuximab; Drug: Carboplatin	Phase 2

Detailed Description:

Primary Objective:To establish the response rate using RECIST 1 criteria to weekly TPC in patients with metastatic or relapsed squamous cell carcinoma of the head and neck Secondary Objective: To establish the safety profile, progression free and overall survival of weekly TPC in this patient population.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Weekly Docetaxel, Cisplatin, and Cetuximab (TPC) in Palliative Treatment of Patients With SCCHN
• Study Start Date: October 2011
• Actual Primary Completion Date: September 11, 2018
• Actual Study Completion Date: August 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Cisplatin + Docetaxel + Cetuximab; Patients will be treated weekly with cisplatin, docetaxel, and cetuximab.

Drug: Docetaxel; 30 mg/m² by intravenous (IV) administration; Other Name: Taxotere; Drug: Cisplatin; 30 mg/m² by intravenous (IV) administration; Other Names: Cisplatinum; Platinol; Drug: Cetuximab; 400 mg/m² by intravenous (IV) administration, thereafter 250 IV; Other Name: Erbitux; Drug: Carboplatin; Area under the free carboplatin plasma concentration versus time curve (AUC)=2 by intravenous (IV) administration; Other Name: Paraplatin

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: 8 weeks ]

   Clinical response for each participant will be assessed after 8 weeks of treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Overall response rate (ORR) was assessed as the sum of the number of participants that experience a complete response (CR) or partial response (PR). The outcome is defined and reported as the number of subjects that responded, a number without dispersion. Other response statuses are included. RECIST v1.1 criteria is defined as follows.

   • Complete Response (CR) = Disappearance of all target lesions
   • Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions
   • Overall Response (OR) = CR + PR
   • Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)
   • Stable disease (SD) = Small changes that do not meet any of the above criteria

Secondary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: 24 months ]

   Progression-free survival (PFS), defined as the duration of time from start of treatment to time of progression or death, was assessed through 24 months, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The outcome is reported as the median time that participants remained free of progression, with 95% confidence interval (CI).

   • Complete Response (CR) = Disappearance of all target lesions
   • Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions
   • Overall Response (OR) = CR + PR
   • Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)
   • Stable disease (SD) = Small changes that do not meet any of the above criteria
2. Overall Survival (OS) [ Time Frame: 24 months ]
   Overall survival (OS) was assessed through 24 months. The outcome is reported as the median time that participants remained alive, with 95% CI.
3. Grade 3, 4, and 5 Related Adverse Events (Toxicities) [ Time Frame: 2 years ]
   Related adverse events are considered toxicities. The outcome was assessed as adverse events and serious adverse events (SAEs per 21CFR§312.32) at least Grade 3, and are reported as the number of toxicities by grade (3, 4 or 5), a number without dispersion.

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA

• Squamous cell carcinoma (SCC) of head and neck (SCCHN), including all pharynx, larynx, oral cavity, skin and para-nasal sinus sites. Patients with SCC of unknown primary presenting in the neck clinically compatible with head and neck mucosal primary sites are eligible.
• If prior chemoradiation, radiation, and/or surgery in the potentially curative setting, > 3 months has elapsed since the end of the potentially curative treatment ended
• If history of other malignancies treated curatively > 1 year prior to enrollment, no evidence of relapse at the time of enrollment
• If brain metastasis, central nervous system (CNS) imaging documents no evidence of CNS progression at least 30 days following definitive CNS treatment (resection or radiation)
• ≥ 16 years old
• Eastern cooperative oncology group (ECOG) Performance Status < 3
• Laboratory value requirements at enrollment:
• Absolute neutrophil count > 1500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 8 g/dL
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) unless liver metastases documented. If so, AST and ALT < 5 x ULN required.
• Total bilirubin < 1.5 x ULN, EXCEPT if Gilbert's syndrome is present. If so, total bilirubin < 2.5 x ULN
• Serum Creatinine < 1.5 mg/dL OR an estimated creatinine clearance from 24 hour urine collection > 50 mL/min
• Peripheral neuropathy < grade 2
• Hearing loss in best ear < grade 2 per Chang criteria if audiogram performed. Formal audiology is not required in patients with no clinical evidence of hearing loss at baseline.
• Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA

• Prior palliative chemotherapy
• Active infections including HIV (EXCEPTION: HIV-positive patients on HAART with undetectable blood HIV levels, or with history or serological evidence of exposure to Hepatitis B without active infection are eligible)
• Prior grade 3 allergic or infusion reactions to docetaxel, cisplatin or cetuximab (EXCEPTION: a history of infusion reactions that were well-tolerated, at physician's discretion)
• Pregnant and/or lactating

Contacts and Locations

Locations

United States, California

University of California Davis Medical Center

Davis, California, United States, 95616

Stanford University, School of Medicine

Stanford, California, United States, 95305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: A. Dimitrios Colevas, MD; Stanford University

  Study Documents (Full-Text)

Documents provided by A. Dimitrios Colevas, Stanford University:

Study Protocol and Statistical Analysis Plan  [PDF] March 26, 2014

Informed Consent Form  [PDF] August 23, 2016

More Information

Publications of Results:

Trieu V, Pinto H, Riess JW, Lira R, Luciano R, Coty J, Boothroyd D, Colevas AD. Weekly Docetaxel, Cisplatin, and Cetuximab in Palliative Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck. Oncologist. 2018 Jul;23(7):764-e86. doi: 10.1634/theoncologist.2017-0618. Epub 2018 Mar 14.

• Responsible Party: A. Dimitrios Colevas, Professor of Medicine (Oncology) and Otolaryngology, Stanford University
• ClinicalTrials.gov Identifier: NCT01437449
• Other Study ID Numbers: IRB-22329; SU-08222011-8290 ( Other Identifier: Stanford University Medical Center ); NCI-2011-03271 ( Other Identifier: CTRP ); ENT0033 ( Other Identifier: OnCore )
• First Posted: September 20, 2011
• Results First Posted: December 17, 2019
• Last Update Posted: December 17, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by A. Dimitrios Colevas, Stanford University:

Quality of Life

Additional relevant MeSH terms:

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Carboplatin; Docetaxel; Cetuximab; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological