Abraxane in Combination With Carboplatin, Erbitux and IMRT for Locally Advanced Squamous Cancer of the Head and Neck

NCT00570674 | Terminated Phase 1 Results DMC

• 1 other identifier: 07-069
• Study Type: interventional
• Target: 29
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the Phase I part of this research study is to determine the safest and most effective dose of Abraxane when given in combination with carboplatin and Erbitux during radiation therapy for head and neck cancer. The purpose of the Phase II part of this study is to determine the effects of the treatment on head and neck cancers, as well as to further study the safety of this treatment.

Conditions

Squamous Cell Carcinoma of the Head and Neck; Basaloid Squamous Cell Carcinoma; Undifferentiated Carcinoma; Adenosquamous Cell Carcinoma

Keywords

SSCHN; Abraxane; IMRT

Outcome Measures

Primary Outcomes (3)

• Abraxane Maximum Tolerated Dose (MTD) [Phase I]

  The Abraxane MTD in combination with carboplatin and concurrent IMRT is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of participants experience a DLT. If no DLTs are observed then the MTD is not reached but the highest dose may then be the recommended phase II dose.

  Adverse event assessments occurred weekly on treatment; The observation period for MTD evaluation incorporated the 7 weeks of treatment.

• Dose Limiting Toxicity (DLT) [Phase I]

  Dose limiting toxicities (DLT) were defined as treatment-related: 1) grade 3-4 non-hematological toxicity excluding untreated nausea, vomiting and diarrhea; dysphagia, esophagitis, mucositis/stomatitis, dermatitis/rash, 2) Grade 3 or greater febrile neutropenia occurring during chemoradiotherapy, 3) Grade 4 neutropenia lasting \>/= 7 days and 4) Grade 3 thrombocytopenia. Grade 4 toxicities resulting in a treatment breaks \> 7 days were considered DLTs.

  Adverse event assessments occurred weekly on treatment; The observation period for DLT evaluation incorporated the 7 weeks of treatment.

• 2-Year Disease-Free Survival [Phase II]

  Disease-free survival (DFS) is defined as the time from registration to the earlier of disease recurrence or death from any cause. Patients alive without a recurrence are censored at the date of last disease evaluation. 2-year disease-free survival is the probability of patients remaining alive and progression-free at 2-years from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target.

  Disease assessments occurred 8-10 weeks following treatment end then every 4-6 weeks (yr 1), every 8-10 weeks (yr 2), quarterly (yr 3) and semiannually up to 2 yrs since last pt enrolled.

Secondary Outcomes (7)

• Overall Response Rate [Phase I]

  The primary re-staging assessment for response occurred 8-10 weeks following completion of treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1).

• 2-Year Overall Survival [Phase I]

  All patients were followed for survival for a minimum of 2 years. Median survival follow-up was 44.7 months (range 10-70) in this study cohort.

• Duration PEG Therapy

  Assessed until time of PEG removal which was up to 18.4 months in this study cohort.

• Change in FACT-H&N Score From Baseline to 4 Months

  baseline and 4 months

• Change in FACT-H&N Score From Baseline to 6 Months

  Baseline and 6 months

Study Arms (5)

Phase I Dose Level 1: ACE-RT

EXPERIMENTAL

Phase I Dose Level 1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. One dose (400 mg/m2 IV) of Erbitux was given prior to start of radiation, then weekly at 250 mg/m2 IV. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.

Drug: Abraxane; Drug: Erbitux; Drug: Carboplatin; Radiation: Intensity Modulated Radiation Therapy

Phase I Dose Level -1: AC-RT

EXPERIMENTAL

Phase I Dose Level -1 participants received Abraxane 20mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.

Drug: Abraxane; Drug: Carboplatin; Radiation: Intensity Modulated Radiation Therapy

Phase I Dose Level 2: AC-RT

EXPERIMENTAL

Phase I Dose Level 2 participants received Abraxane 30mg/m2 IV then carboplatin AUC 1.5 weekly IV during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.

Drug: Abraxane; Drug: Carboplatin; Radiation: Intensity Modulated Radiation Therapy

Phase I Dose Level 3: AC-RT

EXPERIMENTAL

Phase I Dose Level 3 participants received Abraxane 40mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.

Drug: Abraxane; Drug: Carboplatin; Radiation: Intensity Modulated Radiation Therapy

Phase I Dose Level 4: AC-RT

EXPERIMENTAL

Phase I Dose Level 4 participants received Abraxane 50mg/m2 IV then carboplatin AUC 1.5 IV weekly during the period of radiotherapy for a total of 7 weeks. Intensity-modulated radiotherapy (IMRT) was delivered 5 days per week with the prescribed dose of 70 Gy to the gross tumor volume, given in 2 Gy daily fractions for a total of 35 fractions.

Drug: Abraxane; Drug: Carboplatin; Radiation: Intensity Modulated Radiation Therapy

Interventions

Abraxane DRUG

Also known as: paclitaxel

Phase I Dose Level -1: AC-RT; Phase I Dose Level 1: ACE-RT; Phase I Dose Level 2: AC-RT; Phase I Dose Level 3: AC-RT; Phase I Dose Level 4: AC-RT

Erbitux DRUG

Also known as: cetuximab

Phase I Dose Level 1: ACE-RT

Carboplatin DRUG

Also known as: paraplatin

Phase I Dose Level -1: AC-RT; Phase I Dose Level 1: ACE-RT; Phase I Dose Level 2: AC-RT; Phase I Dose Level 3: AC-RT; Phase I Dose Level 4: AC-RT

Intensity Modulated Radiation Therapy RADIATION

Also known as: IMRT

Phase I Dose Level -1: AC-RT; Phase I Dose Level 1: ACE-RT; Phase I Dose Level 2: AC-RT; Phase I Dose Level 3: AC-RT; Phase I Dose Level 4: AC-RT

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven squamous cell carcinoma of th head and neck or its variants. Primary tumor sites eligible include nasopharynx, oral cavity, oropharynx, hypopharynx, larynx, or unknown primary SSCHN. Although they have squamous histology, tumors of the skin, nasal cavity and paranasal sinuses are excluded because their responsiveness to chemotherapy and radiotherapy may differ.
• Stage III or IV disease, without evidence of distant metastasis, according to the American Joint Committee on Cancer.
• Measurable disease, according to RECIST.
• Treatment-naive SSCHN, i.e. no prior chemotherapy, radiotherapy or attempted complete resection.
• \< CTCAE v3.0 Grade 2 neuropathy
• years of age or older
• ECOG Performance Status of 0 or 1
• No active alcohol addiction or other condition that, in the opinion of the study investigators, would interfere with the subject's ability to comply with the treatment plan.
• Lab values as outlined in the protocol
• Negative pregnancy test within 7 days of study entry

You may not qualify if:

• Pregnant or breast-feeding women, or women and men of childbearing potential not willing to use adequate contraception while receiving treatment and for at least 6 months thereafter.
• Symptomatic peripheral neuropathy Grade 2 or greater by CTCAE v3.0
• History of other malignancy within the previous 5 years, except for non-melanoma skin cancer, carcinoma in situ of the cervix, bladder or head and neck.
• Prior therapeutic radiation to the head and neck
• Other serious illness or medical conditions, including but not limited to: unstable cardiac disease or myocardial infarction within 6 months prior to study entry; history of significant neurologic disorder, including advanced dementia or uncontrolled seizure disorder; clinically significant uncontrolled infection; active peptic ulcer disease defined as unhealed or clinically active ulcer; hypercalcemia; active drug addiction including cocaine or intravenous drug use, defined as occuring within 6 months preceding diagnosis; chronic obstructive pulmonary disease; autoimmune disease requiring active therapy; severe psoriasis; chronic uncontrolled diarrhea.
• Patients who experienced involuntary weight loss of more than 20% of their body weight in the two months preceding study entry
• Concurrent treatment with any other anticancer therapy
• Prior therapy that targets the EGFR pathway
• Participation in an investigational drug trial within 30 days of study entry

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Celgene Corporation: collaborator

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Adenosquamous

Interventions

Albumin-Bound Paclitaxel; Paclitaxel; Cetuximab; Carboplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Limitations and Caveats

The phase II portion planned to enroll 34 participants including the expansion cohort but the study did not continue beyond phase I given the importance of HPV status as a prognostic factor to guide treatment decisions.

Results Point of Contact

• Title: Roy B. Tishler, MD
• Organization: Dana-Farber Cancer Institute

RTISHLER@LROC.HARVARD.EDU

617.632.5734

Study Officials

• Roy B. Tishler, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: December 10, 2007
• First Posted: December 11, 2007
• Study Start: November 1, 2007
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 13, 2017
• Results First Posted: December 12, 2016

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share