Weekly Carboplatin, Paclitaxel and Cetuximab Treatment for Patients With Recurrent or Metastatic SCCHN

NCT ID: NCT02124707

Last Updated: 2020-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-16
• Study Completion Date: 2019-10-01

Brief Summary

This is a non-randomized, open-label phase II trial of 38 patients with recurrent or metastatic SCCHN. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 with good organ function and will be treated with six weekly cycles of carboplatin, paclitaxel and cetuximab. Following assessment of response, the treating physician at their discretion may continue to treat with weekly cetuximab as maintenance until disease progression. The study is designed to evaluate whether this regimen improves median overall survival (OS) as compared to an historical control population treated with a platinum plus 5-fluorouracil (5-FU). There is currently no agreed upon first line therapy for recurrent or metastatic SCCHN; regimen options are highly toxic, inconvenient and resource intensive. Our study regimen has been used extensively for induction therapy and off-protocol in palliative care, but treatment outcomes have yet to be defined by a clinical trial.

Detailed Description

Because of their high response rates and low toxicity, the taxane, carboplatin, cetuximab regimens have frequently been adapted for use in the palliative setting. At UNC, we have observed high rates of response, leading to symptomatic benefit and low toxicity. Further, the regimen de-medicalizes the patient's life in several important ways. First, unlike with the EXTREME regimen, no PORT or 4 day infusion is required. Second, the regimen gives only six weeks of cytotoxic therapy. Finally, in our experience there is a low rate of severe toxicity and this, coupled with the high rate of response, may improve quality of life. We are not aware of any presented or published results on the use of this combination in palliative therapy; with the adoption of this regimen in clinical practice, documentation of its benefit via conduct of a clinical trial is needed.

We propose a study designed to detect an improvement in median OS versus a historical control. The control arm from the EXTREME trial achieved a median OS of 7.4 months. We hypothesize that a less toxic and more effective 3-drug regimen will result in improved median OS compared with the control arm from EXTREME (median 7.4 months). The toxicity associated with EXTREME is primarily attributable to the cisplatin and 5FU cytotoxic backbone as its toxicity has been consistent in multiple studies of both palliative therapy and induction therapy. If a 4-month improvement in OS is achieved with acceptable toxicity, we will consider this regimen worth of further study.

Secondary objectives will include characterizing changes in quality of life (QoL), symptoms and toxicities. Patients will be encouraged to co-enroll into the UNCseq protocol for further exploration of associations between genetic changes and clinical outcomes.

Conditions

Head and Neck Cancer; Squamous Cell Carcinoma of the Head and Neck

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carboplatin, Paclitaxel and Cetuximab

A 6 week course of weekly carboplatin, paclitaxel, and cetuximab will be administered to 38 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Once protocol therapy is complete, cetuximab may be continued if the patient and physician agree. Within 3 weeks of the end of protocol therapy, response will be assessed, and if the patient has achieved at least stable disease, the treating physician may continue to treat with weekly cetuximab at their discretion until disease progression. Patients will be followed for a maximum of 3 years after the end of the 6 week treatment phase.

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

400mg/m2 IV (in the vein) on day 1 of week 1 and 250mg/m2 IV (in the vein) on day 1 of weeks 2-6. Patients with stable disease may continue on maintenance therapy at the 250mg/m2 dose until disease progression.

Paclitaxel

Intervention Type: DRUG

135mg/m2 IV (in the vein) on day 1 of each 1 week for 6 weeks.

Carboplatin

Intervention Type: DRUG

AUC2, IV (in the vein) on day 1 of each 1 week for 6 weeks.

Interventions

Cetuximab

400mg/m2 IV (in the vein) on day 1 of week 1 and 250mg/m2 IV (in the vein) on day 1 of weeks 2-6. Patients with stable disease may continue on maintenance therapy at the 250mg/m2 dose until disease progression.

Intervention Type: DRUG

Paclitaxel

135mg/m2 IV (in the vein) on day 1 of each 1 week for 6 weeks.

Intervention Type: DRUG

Carboplatin

AUC2, IV (in the vein) on day 1 of each 1 week for 6 weeks.

Intervention Type: DRUG

Other Intervention Names

Erbitux; Taxol; Paraplatin

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old
• Histologically or cytologically confirmed recurrent or metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN). All primary sites are eligible excluding WHO type III or EBV nasopharyngeal (WHO type I and WHO type II allowed as long as they are EBV negative)
• ECOG performance status 0-1
• Adequate organ and marrow function as defined below. Laboratory tests should be completed within 14 days prior to registration: ANC greater than or equal to 1,500/mm3, Platelets greater than or equal to 100,000/mm3, HgB greater than 9g/dL (acceptable to reach this by transfusion), Total bilirubin less than or equal to 1.5mg/dL, Albumin greater than 2.5 g/dL, AST(SGOT)/ALT(SGPT) less than or equal to 2.5X institutional upper limit of normal, alkaline phosphatase less than or equal to 2.5 x upper limit of normal, GFR greater than 30 mL/min (by standard Cockroft and Gault formula or measured via 24 hour urine collection)
• Women of childbearing potential (WOCBP) with negative serum or urine pregnancy test within 7 days of D1 of treatment
• WOCBP and men must agree to use adequate contraception prior to study entry and for duration of treatment under this protocol; adequate contraception is defined as any medically recommended method (or combination of methods) per standard of care.
• Cancer must be considered incurable by the treating clinician
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

• History of prior cumulative exposure to > 300mg/m2 cisplatin, AUC of 18 of carboplatin, or their combined equivalent within one year prior to enrollment
• Surgery or radiation within the four weeks prior to D1 of treatment under this protocol
• Prior systemic chemotherapy unless it was part of definitive-intent (curative intent) treatment more than 6 months before study entry
• Other active, invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years; localized squamous cell carcinoma of the skin, basal-cell carcinoma of the skin, carcinoma in-situ of the cervix, or other malignancies requiring locally ablative therapy only will not result in exclusion
• Pregnant or lactating female

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jared Weiss, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Bon Secours Virginia Health System

Midlothian, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.unclineberger.org

UNC Lineberger Comprehensive Cancer Center

Other Identifiers

LCCC 1330

Identifier Type: -

Identifier Source: org_study_id