Docetaxel/Cisplatin/5-Fluorouracil (TPF) Human Papillomavirus (HPV) Squamous Cell Carcinoma Study

NCT01221753 | Terminated Phase 2 Results DMC

• 1 other identifier: 10-038
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

In this research study, the investigators are studying whether a reduced dose of radiation when given with standard doses of chemotherapy can reduce side effects without compromising control of the cancer. An approved treatment for squamous cell carcinoma of the head and neck is initial chemotherapy followed by radiation and chemotherapy together. This treatment is effective but has many immediate and long-term side effects. People who have squamous cell carcinoma of the head and neck (SSCHN) that is related to an infection by the human papillomavirus (HPV) have been shown to have a high response to this treatment along with a high cure rate. The investigators think that by reducing the intensity of this treatment, they may be able to reduce immediate and long-term side effects which may lead to long term improvements in quality of life and function.

Conditions

Squamous Cell Carcinoma of the Head and Neck; Human Papilloma Virus

Keywords

SSCHN; HPV; IMRT

Outcome Measures

Primary Outcomes (1)

• 2-Year Local-Regional Control Rate

  2-year local-regional control rate is defined as the proportion of participants who achieve confirmed stable disease (SD) or better by 2-years post study registration based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. SD is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  Follow-up for response continued until first progression. Disease assessments occurred at completion of induction cycle 3 along with months 12, 18 and 24 post study registration.

Secondary Outcomes (1)

• 4-y Overall Survival Rate

  Patients were followed for survival up to 5 years from study entry. Patients alive have been followed for a mean of 55 months (range 52-60 months).

Study Arms (1)

TPF Induction Chemotherapy followed by Chemoradiotherapy

EXPERIMENTAL

Patients received 3 cycles (21 days each) of TPF induction chemotherapy: docetaxel 75 mg/m2 IV day 1; cisplatin 100 mg/m2 IV day 1 (carboplatin substitute permitted); 5-FU 1000 mg/m2/day IV pump continuous days 1-4. Concurrent chemoradiotherapy followed 4-6 weeks after day 1 of cycle 3 TPF induction: cetuximab 400 mg/m2 IV loading dose 1 week prior and 250 mg/m2 IV weekly (panitumumab substitute permitted); carboplatin AUC 1.5 (Calvert formula) IV weekly; Intensity modulated radiation therapy (IMRT)-response based dosing for 6-7 weeks.

Drug: docetaxel; Drug: cisplatin; Drug: 5-FU; Radiation: IMRT; Drug: cetuximab; Drug: carboplatin

Interventions

docetaxel DRUG

Also known as: Taxotere, Docefrez

TPF Induction Chemotherapy followed by Chemoradiotherapy

cisplatin DRUG

Given intravenously on day 1 of each cycle

Also known as: Platinol-AQ

TPF Induction Chemotherapy followed by Chemoradiotherapy

5-FU DRUG

Also known as: 5-fluorouracil

TPF Induction Chemotherapy followed by Chemoradiotherapy

IMRT RADIATION

Also known as: Intensity modulated radiation therapy

TPF Induction Chemotherapy followed by Chemoradiotherapy

cetuximab DRUG

Also known as: Erbitux

TPF Induction Chemotherapy followed by Chemoradiotherapy

carboplatin DRUG

Also known as: Paraplatin

TPF Induction Chemotherapy followed by Chemoradiotherapy

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 confirmed squamous cell carcinoma of the oropharynx or unknown primary that is HPV 16 positive as determined by ISH and p16 positive as determined by IHC.
• Stage 3 or 4 disease without evidence of distant metastases
• At least one evaluable or uni- or bi-dimensionally measurable lesion by RECIST 1.1 criteria
• years of age or older
• No previous surgery, radiation therapy or chemotherapy for SSCHN is allowed at time of study entry
• ECOG Performance Status of 0 or 1
• No active alcohol addiction
• Adequate bone marrow, hepatic and renal function as defined in the protocol
• Women of child-bearing potential must have a negative pregnancy test within 7 days of starting treatment

You may not qualify if:

• Pregnant or breast feeding women or women and men of childbearing potential not willing to use adequate contraception while on treatment and for at least 3 months after
• Previous or current malignancies at other sites
• Symptomatic peripheral neuropathy of grade 2 or greater
• Symptomatic altered hearing greater than grade 2
• Other serious illnesses or medical conditions
• Patients that have experienced an involuntary weight loss of more than 25% of their body weight in the 2 months preceding study entry
• Concurrent treatment with any other anticancer therapy
• Participation in an investigational trial within 30 days of study entry

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Docetaxel; Cisplatin; Fluorouracil; Radiotherapy, Intensity-Modulated; Cetuximab; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes

Limitations and Caveats

The study was terminated early due to weak accrual. Because of the designation of study completed at the institution conducting the study, data collected systematically on the case report forms were not accessible for results reporting.

Results Point of Contact

• Title: Robert Haddad, MD
• Organization: Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA02215

robert_haddad@dfci.harvard.edu

617-632-3090

Study Officials

• Robert Haddad, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncology

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: October 15, 2010
• Study Start: July 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2017
• Last Updated: December 6, 2017
• Results First Posted: December 6, 2016

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)