Cetuximab + Taxotere With Low Dose Fractionated Radiation for Head and Neck Carcinoma

Phase II Trial Using Erbitux+ Taxotere With Low Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck Carcinoma

Whether low-dose radiation in addition to Taxotere and Erbitux improves the response rate of patients with recurrent unresectable head and neck squamous cell carcinoma.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Cancer; Recurrent Disease; Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Erbitux; Drug: Taxotere; Radiation: Low Dose Fractionated Radiation Therapy

Detailed Description

The investigator's approach is based on the following reasons:

• Low dose hyper-radiation sensitivity response will be significantly enhanced in Taxotere- induced G2/M cell cycle arrest.
• LDFRT will render enhanced bax activation mediated mode of cell death.
• Erbitux will arrest the cells in G1/G0 phase leading to p21-mediated mode of cell death.
• The toxicity profile is expected to be minimal.

Based on the above mentioned reasons, we propose this novel schema of treatment in recurrent SCCHN.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have pathologically confirmed recurrence (reappearance of previously cleared) squamous cell cancer primary in the upper aerodigestive tract .Patients may have experienced more than one recurrence as long as the first recurrence occurred ≥ 6 months following the end of the prior RT.
2. The recurrence must have defined bi- or uni-dimensional measurements.
3. Recurrence must be confined to the head and neck above the clavicles (loco-regional recurrence).
4. The patient must not be a candidate for surgical resection.
5. Patients must be at least 6 months from completion of prior chemotherapy and radiation therapy.
6. Patients may have received prior chemotherapy as a component of their primary treatment, but not for recurrent disease.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
8. Granulocytes ≥ 1500/mm3, platelets ≥ 100,000/mm3, serum bilirubin ≤ 1.5 mg/dl, creatinine < 1.5 mg/dl within 3 weeks prior to registration.
9. Liver Function Tests (LFTs) ≤ 2 x normal (serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic-pyruvic transaminase (SGPT)/Alkaline Phosphatase). If > 2 x normal, liver ultrasound or CT is required to exclude metastases. If negative for metastases, patients are eligible.
10. Patients must sign a study-specific informed consent form prior to study entry.

Exclusion Criteria:

1. Distant metastases outside of the head and neck.
2. Primary disease in the nasopharynx or the salivary gland.
3. Other concurrent invasive malignancies.
4. Prior invasive malignancy unless disease free for at least two years (except prior in situ malignancies, e.g. cervix, breast, non-melanomatous skin cancer, etc. are permissible).
5. Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival.
6. Pre-existing grade ≥ 2 peripheral sensory neuropathy
7. Pregnant and nursing women are excluded because of the potential teratogenic effects and potential unknown effects on nursing newborns.
8. Prior history of sever hypersensitivity reaction to Docetaxol, Cetuximab or a drug with formulated with Polysorbate 80.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Erbitux, Taxotere, LD Fractionated RT; Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT)

Drug: Erbitux; Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere.; Other Names: Cetuximab; Drug: Taxotere; Taxotere : 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7.; Other Names: Docetaxel; Radiation: Low Dose Fractionated Radiation Therapy; Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.; Other Names: LDFRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) of Participants	ORR is defined as the rate of study participants achieving complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria.	Up to 6 months from End of Treatment, about 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Study Participants Experiencing Treatment-Related Toxicity	Assess the safety profile (acute and late toxicities) of the proposed treatment. Number of study participants experiencing treatment-related acute and late toxicity: Acute toxicity is defined as toxicity occurring within 90 days of start of therapy.; Late/Long-term toxicity defined as toxicity occurring more than 90 days after start of therapy.	Up to 6 years
Estimated Progression-Free Survival (PFS)	Progression-free survival (PFS) is defined of the length of time from the start date of treatment to the earliest documented occurrence of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. In the absence of an event constituting failure, follow up time will be censored at the date of last disease assessment.	Up to 6 years
Estimated Overall Survival (OS)	Overall survival (OS) is defined as the length of time from the start of treatment that study participants diagnosed with the disease are still alive. OS will be measured from the start date of treatment to the date of death or last contact (censored observations).	Up to 6 years

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Matthew C Abramowitz, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2013
• Primary Completion (Actual): June 7, 2016
• Study Completion (Actual): June 7, 2016

Study Registration Dates

• First Submitted: February 14, 2013
• First Submitted That Met QC Criteria: February 19, 2013
• First Posted (Estimate): February 20, 2013

Study Record Updates

• Last Update Posted (Actual): May 11, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Squamous Cell Carcinoma; Recurrent; SCCHN
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Recurrence; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Cetuximab
• Other Study ID Numbers: 20090467

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO