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Nab-Paclitaxel, Cisplatin, and Cetuximab With Concurrent Radiation Therapy for Locally Advanced Head and Neck Cancer

Primary Purpose

Head and Neck Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cetuximab

Cisplatin

Nab-Paclitaxel

intensity-modulated radiation therapy

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, tongue cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Histologically confirmed squamous cell carcinoma of the oropharynx, hypopharynx, or larynx
- Diagnosis based on the primary lesion and/or lymph nodes
- Stage III or IV disease (T2, N2-3, M0 or T3-4, any N, M0)
No primary tumor of the oral cavity, nasopharynx, sinuses, or salivary glands
No distant metastasis by chest x-ray, CT scan, or PET/CT scan within the past 6 weeks

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
ANC > 1,500/mm^3
Platelet count > 100,000/mm^3
Hemoglobin > 9.0 g/dL (transfusion or other intervention to achieve hemoglobin > 8.0 g/dL allowed)
Bilirubin ≤ 1.5 mg/dL
AST, ALT, and AP ≤ 2.5 times upper limit of normal
Serum creatinine ≤ 1.5 mg/dL
Creatinine clearance ≥ 50 mL/min
None of the following electrolyte abnormalities grade 3-4 by CTCAE v 3.0:
- Calcium < 7 mg/dL or > 12.5 mg/dL
- Glucose < 40 mg/dL or > 250 mg/dL
- Magnesium < 0.9 mg/dL or > 3 mg/dL
- Potassium < 3 mmol/L or > 6 mmol/L
- Sodium < 130 mmol/L or > 155 mmol/L
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other prior invasive malignancy, except for nonmelanomatous skin cancer, unless disease-free for ≥ 3 years
No prior allergic reaction to study drugs
No active cardiac disease, defined as any of the following:
- Unstable angina
- Uncontrolled hypertension
- Myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass graft or percutaneous transluminal coronary angioplasty)
- Uncontrolled arrhythmia
- Congestive heart failure
- Three or more heart-related hospitalizations within the past year
No severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year
No AIDS
No pre-existing peripheral sensory neuropathy ≥ grade 2
No concurrent medical illnesses that would impair patient tolerance to therapy or limit survival

PRIOR CONCURRENT THERAPY:

No prior systemic chemotherapy for this cancer
- Prior systemic chemotherapy for a different cancer allowed
No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields
No prior initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease)
At least 48 hours since prior and no concurrent granulocytic growth factors (e.g., filgrastim [G-CSF]) during radiotherapy
No concurrent erythropoietic growth factors (e.g., darbepoetin, erythropoietin)

Sites / Locations

Baylor Research Institute
University of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

arm one

Arm Description

Nab-Paclitaxel, Cisplatin, Cetuximab, intensity-modulated radiation therapy

Outcomes

Primary Outcome Measures

Phase I Maximum Tolerated Dose of Nab-Paclitaxel

Seven participants were assigned nab-paclitaxel in dose of 25mg/m^2. Five participants were assigned nab-paclitaxel in dose of 20mg/m^2.

Phase II 2-year Progression-free Survival

Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The primary endpoint of 2-year progression-free survival was measured from the date of enrollment to the first occurrence of new metastatic lesion, objective tumor progression, or death.

Secondary Outcome Measures

Phase II 2-year Local Control

Local control is defined as the arrest cancer growth at the site of origin. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions

Phase II 2-year Overall Survival

median follow-up 24 months for 34 patients

Full Information

NCT ID

NCT00851877

First Posted

February 25, 2009

Last Updated

August 19, 2020

Sponsor

University of Texas Southwestern Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT00851877

Brief Title

Nab-Paclitaxel, Cisplatin, and Cetuximab With Concurrent Radiation Therapy for Locally Advanced Head and Neck Cancer

Official Title

A Phase I/II Study of Nab-paclitaxel, Cisplatin and Cetuximab With Concurrent Radiation Therapy for Local-regionally Advanced Head-and-neck Squamous Cell Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

March 1, 2009 (Actual)

Primary Completion Date

October 1, 2013 (Actual)

Study Completion Date

August 3, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Texas Southwestern Medical Center

4. Oversight

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Paclitaxel albumin-stabilized nanoparticle formulation may make tumor cells more sensitive to radiation therapy. Giving radiation therapy and paclitaxel albumin-stabilized nanoparticle formulation together with cisplatin and cetuximab may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of paclitaxel albumin-stabilized nanoparticle formulation when given together with cisplatin, cetuximab, and radiation therapy to see how well they work in treating patients with locally advanced stage III or stage IV head and neck cancer.

Detailed Description

OBJECTIVES: Primary To determine the maximum tolerated dose of paclitaxel albumin-stabilized nanoparticle formulation when combined with cisplatin, cetuximab, and radiotherapy in patients with local-regionally advanced squamous cell carcinoma of the head and neck. (Phase I) To evaluate the disease-free survival of patients treated with this regimen. (Phase II) Secondary To identify dose-limiting toxicities in these patients treated with this regimen. (Phase I) To assess the safety and tolerability of this regimen. (Phases I and II) To assess progression-free survival and survival of patients treated with this regimen. (Phase I) To assess overall survival in patients treated with this regimen. (Phase II) To assess response rates in patients treated with this regimen. (Phases I and II) OUTLINE: This is a multicenter, phase I dose-escalation study of paclitaxel albumin-stabilized nanoparticle formulation followed by a phase II study. Patients receive cetuximab IV over 120 minutes in week 1. Patients then receive cetuximab IV over 60 minutes, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes, and cisplatin IV over 60 minutes once weekly in weeks 2-8. Patients also undergo 3D conformal or intensity-modulated radiotherapy over 30 minutes on days 1-5 in weeks 2-8. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 4 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Cancer

Keywords

stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, tongue cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

37 (Actual)

8. Arms, Groups, and Interventions

Arm Title

arm one

Arm Type

Experimental

Arm Description

Nab-Paclitaxel, Cisplatin, Cetuximab, intensity-modulated radiation therapy

Intervention Type

Biological

Intervention Name(s)

Cetuximab

Intervention Description

Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

Platinol

Intervention Description

Cisplatin is an anti-cancer chemotherapy drug

Intervention Type

Drug

Intervention Name(s)

Nab-Paclitaxel

Other Intervention Name(s)

Abraxane

Intervention Description

paclitaxel albumin-stabilized nanoparticle formulation

Intervention Type

Radiation

Intervention Name(s)

intensity-modulated radiation therapy

Intervention Description

intensity-modulated radiation therapy

Primary Outcome Measure Information:

Title

Phase I Maximum Tolerated Dose of Nab-Paclitaxel

Description

Seven participants were assigned nab-paclitaxel in dose of 25mg/m^2. Five participants were assigned nab-paclitaxel in dose of 20mg/m^2.

Time Frame

90 days

Title

Phase II 2-year Progression-free Survival

Description

Time Frame

2 year

Secondary Outcome Measure Information:

Title

Phase II 2-year Local Control

Description

Time Frame

2 year

Title

Phase II 2-year Overall Survival

Description

median follow-up 24 months for 34 patients

Time Frame

2 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the oropharynx, hypopharynx, or larynx Diagnosis based on the primary lesion and/or lymph nodes Stage III or IV disease (T2, N2-3, M0 or T3-4, any N, M0) No primary tumor of the oral cavity, nasopharynx, sinuses, or salivary glands No distant metastasis by chest x-ray, CT scan, or PET/CT scan within the past 6 weeks PATIENT CHARACTERISTICS: Zubrod performance status 0-1 ANC > 1,500/mm^3 Platelet count > 100,000/mm^3 Hemoglobin > 9.0 g/dL (transfusion or other intervention to achieve hemoglobin > 8.0 g/dL allowed) Bilirubin ≤ 1.5 mg/dL AST, ALT, and AP ≤ 2.5 times upper limit of normal Serum creatinine ≤ 1.5 mg/dL Creatinine clearance ≥ 50 mL/min None of the following electrolyte abnormalities grade 3-4 by CTCAE v 3.0: Calcium < 7 mg/dL or > 12.5 mg/dL Glucose < 40 mg/dL or > 250 mg/dL Magnesium < 0.9 mg/dL or > 3 mg/dL Potassium < 3 mmol/L or > 6 mmol/L Sodium < 130 mmol/L or > 155 mmol/L Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other prior invasive malignancy, except for nonmelanomatous skin cancer, unless disease-free for ≥ 3 years No prior allergic reaction to study drugs No active cardiac disease, defined as any of the following: Unstable angina Uncontrolled hypertension Myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass graft or percutaneous transluminal coronary angioplasty) Uncontrolled arrhythmia Congestive heart failure Three or more heart-related hospitalizations within the past year No severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year No AIDS No pre-existing peripheral sensory neuropathy ≥ grade 2 No concurrent medical illnesses that would impair patient tolerance to therapy or limit survival PRIOR CONCURRENT THERAPY: No prior systemic chemotherapy for this cancer Prior systemic chemotherapy for a different cancer allowed No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields No prior initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease) At least 48 hours since prior and no concurrent granulocytic growth factors (e.g., filgrastim [G-CSF]) during radiotherapy No concurrent erythropoietic growth factors (e.g., darbepoetin, erythropoietin)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hak Choy, MD

Organizational Affiliation

Simmons Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Baylor Research Institute

City

Dallas

State/Province

Texas

ZIP/Postal Code

75204

Country

United States

Facility Name

University of Texas Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75239

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Nab-Paclitaxel, Cisplatin, and Cetuximab With Concurrent Radiation Therapy for Locally Advanced Head and Neck Cancer

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