Cisplatin, Paclitaxel Albumin-Stabilized Nanoparticle Formulation, and Cetuximab in Treating Patients with Head and Neck Squamous Cell Carcinoma That Is Metastatic, Locally Recurrent, or Cannot Be Removed by Surgery

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IITreatmentActive18 and over201410073
NCI-2014-02222, NCT02270814

Trial Description

Summary

This phase II trial studies how well cisplatin, paclitaxel albumin-stabilized nanoparticle formulation, and cetuximab work in treating patients with head and neck squamous cell carcinoma that has spread to another place in the body, has come back locally, or cannot be removed by surgery. Drugs used in chemotherapy, such as cisplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. Giving cisplatin, paclitaxel albumin-stabilized nanoparticle formulation, and cetuximab may be an effective treatment for cancer of the oral cavity, oropharynx, larynx, or hypopharynx.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine progression-free survival in patients receiving cisplatin (or carboplatin), nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation), and cetuximab as first-line therapy for treatment of incurable head and neck squamous cell carcinoma (HNSCC).

SECONDARY OBJECTIVES:

I. To determine overall survival in patients receiving cisplatin (or carboplatin), nab-paclitaxel, and cetuximab as first-line therapy for treatment of incurable HNSCC.

II. To determine response rates in patients receiving cisplatin (or carboplatin), nab-paclitaxel, and cetuximab as first-line therapy for treatment of incurable HNSCC.

III. To evaluate the instances of grade 3 and 4 adverse events (using Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) in patients receiving cisplatin (or carboplatin), nab-paclitaxel, and cetuximab as first-line therapy for treatment of incurable HNSCC.

IV. To characterize the quality of life of patients receiving cisplatin (or carboplatin), nab-paclitaxel, and cetuximab as first-line therapy for treatment of incurable HNSCC.

V. To determine progression-free survival in patients receiving maintenance therapy with nab-paclitaxel and cetuximab for treatment of incurable HNSCC.

TERTIARY OBJECTIVES:

I. To perform mutational analysis (phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K] pathway and Harvey rat sarcoma viral oncogene homolog [H-Ras]) on tumor tissue collected from patients with incurable HNSCC.

II. To perform immunohistochemical analyses (epidermal growth factor receptor [EGFR], v-akt murine thymoma viral oncogene homolog 1 [AKT], phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [PIK3CA], phosphatase and tensin homolog [PTEN], MET proto-oncogene, receptor tyrosine kinase [MET], and protein [p]S6 kinase) on tumor tissue collected from patients with incurable HNSCC.

III. To perform immune activation analyses (tumor infiltrating lymphocytes [TIL] markers, programmed cell death [PD]-ligand [L]1) on tumor tissue collected from patients with incurable HNSCC.

OUTLINE:

Patients receive cisplatin* intravenously (IV) over 60 minutes or carboplatin IV over 30 minutes on day 1, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and cetuximab IV on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients receive maintenance chemotherapy comprising paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1 and 8 and cetuximab IV on days 1, 8, and 15. Maintenance treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

*NOTE: Cisplatin is preferred, but carboplatin may be given if the patient has a prior intolerance to cisplatin or at the discretion of the treating physician.

After completion of study treatment, patients are followed up every 3 months.

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed incurable HNSCC of the oral cavity, oropharynx, larynx, hypopharynx, and/or level 1-3 neck node with non-skin squamous cell carcinoma (SCC) and unknown primary; “incurable” is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection)

Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with computed tomography (CT) scan, as >= 20 mm by chest x-ray, or >= 10 mm with calipers by clinical exam per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Eastern Cooperative Oncology Group (ECOG) performance status =< 1

Leukocytes >= 3,000/mcL

Absolute neutrophil count >= 1,500/mcl

Platelets >= 100,000/mcl

Total bilirubin =< 1.5 mg/dL

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (IULN), unless bone metastasis is present in the absence of liver metastasis

Alkaline phosphatase =< 2.5 x IULN, unless bone metastasis is present in the absence of liver metastasis

Creatinine at or below IULN (males 0.7-1.30 mg/dl; females 0.6-1.10 mg/dl) OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

At least 4 months since completion of curative therapy, if given previously

Availability of diagnostic tumor tissue specimens for correlative studies

Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after completing treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately

Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria:

Prior systemic therapy for incurable disease

Grade 2 or higher peripheral neuropathy at screening

A history of other malignancy =< 2 years previous; exceptions are malignancies with a negligible risk of metastasis or death (e.g., expected 5-year overall survival [OS] > 90%) that were treated with an expected curative outcome, such as squamous cell carcinoma of the skin, in-situ carcinoma of the cervix uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, incidental histological finding of prostate cancer (tumor, node, metastasis [TNM] stage of T1a or T1b) or synchronous head and neck (H&N) primaries

Currently receiving any other investigational agents

Known brain metastases

A history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, nab-paclitaxel, or other agents used in the study; previous grade 1 or 2 allergic reaction to cetuximab is permissible

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Pregnant and/or breastfeeding; patient must have a negative pregnancy test within 72 hours of start of study treatment

Known human immunodeficiency virus (HIV)-positivity on combination antiretroviral therapy

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Siteman Cancer Center at Washington University

  • National Cancer Institute
Douglas Ray Adkins, Principal Investigator

Trial Sites

U.S.A.

Missouri
Saint Louis

Siteman Cancer Center at Washington University

Douglas Ray Adkins
Ph: 314-362-5654
Email: dadkins@wustl.edu

Douglas Ray Adkins
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT02270814

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.