A Phase I/II Study of Radiation Therapy, Paclitaxel Poliglumex and Cetuximab in Advanced Head and Neck Cancer

NCT00660218 | Completed Phase 1 DMC

• 1 other identifier: X90003
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

This study involves two phases. Phase I of this study is designed to find out the maximum dose of paclitaxel poliglumex which can be safely given to subjects when combined with cetuximab and radiotherapy in head and neck cancer. Once the maximum safe dose of paclitaxel poliglumex is found, Phase II of the study will continue to find out whether the addition of paclitaxel poliglumex increases tumor response and survival compared to treatment with cetuximab and radiotherapy alone. An additional 20 patients have been added, to balance data. These patients must be HPV negative.

Conditions

Carcinoma, Squamous Cell

Keywords

Stage III and IV head and neck cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: the maximum tolerated dose of paclitaxel poliglumex in combination with radiotherapy and cetuximab for locally advanced head and neck cancer

  30 days

• Phase II: the rate of locoregional control at one year

  1 year

Secondary Outcomes (5)

• The overall response rate (complete and partial response)

  1 month following treatment and then every 4 months

• The acute and late toxicity profile associated with the study regimen

  1 month following treatment and then every 4 months

• The duration of control of locoregional disease

  1 month following treatment and then every 4 months

• Overall survival, disease-free survival, and distant relapse rates

  1 month following treatment and then every 4 months

• Tissue PPX accumulation, level of cathepsin B, and estrogen receptor expression

  At time of locoregional disease progression

Study Arms (1)

Radiation therapy, cetuximab, paclitaxel poliglumex

EXPERIMENTAL

Radiation therapy to 69.96 Gy, 2.12 Gy per day for 33 treatments, starting week 2. Cetuximab loading dose of 400 mg/m² week 1, 250 mg/m² weekly for 7 weeks. Paclitaxel poliglumex starting week 2 40 mg/m².

Drug: paclitaxel poliglumex; Biological: cetuximab; Radiation: radiation therapy (IMRT or 3D-CRT)

Interventions

paclitaxel poliglumex DRUG

Phase I: 40 mg/m2 IV weekly in Cohort 1 (first 3 subjects), escalating in increments of 10 mg/m2 for Cohorts 2 through 5 (3 subjects each) until the maximum tolerated dose (up to 80 mg/m2 IV weekly) is established; Phase II: MTD mg/m2 IV weekly as established in Phase I (24 additional subjects)

Also known as: PPX, Xyotax, CT-2103

Radiation therapy, cetuximab, paclitaxel poliglumex

cetuximab BIOLOGICAL

400 mg/m2 IV loading dose one week prior to starting other study treatments, then 250 mg/m2 IV weekly on same day as paclitaxel poliglumex

Also known as: C225, Erbitux

Radiation therapy, cetuximab, paclitaxel poliglumex

radiation therapy (IMRT or 3D-CRT) RADIATION

radiation therapy to the head and neck, consisting of 33 daily fractions of 2.12 Gy for a total of 69.96 Gy, to begin the same day as paclitaxel poliglumex

Radiation therapy, cetuximab, paclitaxel poliglumex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histological proof (from the primary lesion and/or cervical lymph node) of squamous carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, or unknown primary.
• Patients should have stage III or IV disease
• Patients must have ECOG Performance Status of 0-1
• Patients must be \>/= 18 years of age
• Patients must have measurable disease
• Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC) of \>/= 1500 cells/mm3, platelet count of \>/= 100,000 cells/ mm3; adequate hepatic function with bilirubin \</= 1.5mg/dl, AST and ALT \</= 2x the upper limit of normal; serum creatinine \</= 1.5mg/dl, creatinine clearance \>/= 50 ml/min and INR 0.8 - 1.2
• Patients must sign a study specific informed consent form prior to study entry
• Final 20 subjects must be HPV negative

You may not qualify if:

• Histology other than squamous cell carcinoma
• Evidence of metastases (below the clavicle or distant) by clinical or radiographic examinations for phase II study subjects
• History of malignancy other than non-melanoma skin cancer
• Prior chemotherapy or anticancer biologic therapy for any type of cancer, or prior radiotherapy to the head and neck region except for radioactive iodine therapy
• Prior history of allergy or hypersensitivity to cetuximab or paclitaxel
• Weight loss \> 10% in the past three months
• Patients with uncontrolled intercurrent disease
• Patients with currently active malignancy
• Pregnant or lactating women
• Female patients of childbearing potential who are unwilling to practice adequate contraception during study treatment and for two months after the last administration of study drug

Sponsors & Collaborators

• State University of New York - Upstate Medical University: lead
• CTI BioPharma: collaborator

Study Sites (1)

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Head and Neck Neoplasms

Interventions

paclitaxel poliglumex; Cetuximab; Radiotherapy; Radiotherapy, Intensity-Modulated; Radiotherapy, Conformal

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Radiotherapy, Computer-Assisted

Study Officials

• Seung Shin Hahn, MD

  State University of New York - Upstate Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 11, 2008
• First Posted: April 17, 2008
• Study Start: March 1, 2008
• Primary Completion: December 1, 2016
• Study Completion: April 1, 2017
• Last Updated: November 8, 2021

Record last verified: 2021-10

Locations

US (1)