Erlotinib and Radiation Therapy With or Without Cisplatin in Treating Patients With Mouth or Throat Cancer

NCT00049166 | Completed Phase 1

• 6 other identifiers: NCI-2012-03155NCI-5375JHOC-20020723JHOC-J01745375U01CA070095
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I trial to study the effectiveness of combining erlotinib with radiation therapy with or without cisplatin in treating patients who have advanced mouth or throat cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with radiation therapy with or without cisplatin may kill more tumor cells.

Conditions

Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of cisplatin, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0

  Summarized using descriptive statistics.

  Up to 7 weeks

Secondary Outcomes (6)

• Time to progression

  Up to 2 years

• Pharmacokinetics in terms of steady state concentration (Css, min)

  Up to 10 weeks

• Percent change in standardized uptake value (SUV) corrected for lean body mass

  Up to 14 days

• Biological response for each individual patient as defined by determination of the proportional variation of each biomarker

  Up to 2 years

• Relationship between time to treatment failure versus variations in the biomarkers

  Up to 2 years

Study Arms (2)

Regimen A (erlotinib hydrochloride, IMRT)

EXPERIMENTAL

Patients receive oral erlotinib once daily. Beginning on day 15, patients also undergo IMRT once daily 5 days a week for 7 weeks. Patients in both regimens continue to receive erlotinib until the last day of IMRT (patients already in the maintenance phase of this study as of 5/11/04 continue to receive erlotinib once daily for up to 2 years) in the absence of disease progression or unacceptable toxicity. In both regimens, cohorts of 3-6 patients receive escalating doses of erlotinib until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Drug: erlotinib hydrochloride; Radiation: intensity-modulated radiation therapy; Other: laboratory biomarker analysis

Regimen B (erlotinib hydrochloride, cisplatin, IMRT)

EXPERIMENTAL

Patients receive oral erlotinib and undergo IMRT as in regimen A. Patients also receive cisplatin IV over 20 minutes on each day of radiotherapy. Patients in both regimens continue to receive erlotinib until the last day of IMRT (patients already in the maintenance phase of this study as of 5/11/04 continue to receive erlotinib once daily for up to 2 years) in the absence of disease progression or unacceptable toxicity. In both regimens, cohorts of 3-6 patients receive escalating doses of erlotinib until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Drug: erlotinib hydrochloride; Drug: cisplatin; Radiation: intensity-modulated radiation therapy; Other: laboratory biomarker analysis

Interventions

erlotinib hydrochloride DRUG

Given orally

Also known as: CP-358,774, erlotinib, OSI-774

Regimen A (erlotinib hydrochloride, IMRT); Regimen B (erlotinib hydrochloride, cisplatin, IMRT)

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Regimen B (erlotinib hydrochloride, cisplatin, IMRT)

intensity-modulated radiation therapy RADIATION

Undergo intensity modulated radiation therapy

Also known as: IMRT

Regimen A (erlotinib hydrochloride, IMRT); Regimen B (erlotinib hydrochloride, cisplatin, IMRT)

laboratory biomarker analysis OTHER

Correlative studies

Regimen A (erlotinib hydrochloride, IMRT); Regimen B (erlotinib hydrochloride, cisplatin, IMRT)

Eligibility Criteria

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

You may qualify if:

• Patients with clinical findings consistent with a diagnosis of squamous cell carcinoma of the OC or OP, as determined by the head and neck surgeon, may be recruited to the study prior to diagnostic biopsy; patients must have a histologically confirmed diagnosis of squamous cell carcinoma of OC or OP prior to proceeding with treatment
• Oropharyngeal sites include base of tongue, tonsil, soft palate, and oropharyngeal wall
• Oral cavity sites include oral tongue, buccal mucosa, floor of mouth, retromolar trigone, alveolar ridge, hard palate and mucosal lip
• Patients must be AJCC stage II (T2N0) or III (T1-2N1) (AJCC fifth edition, 1997) for part A of the study, and must be AJCC stage III (T3N 0-1) or IV (T1-4N2-3M0, T4N0-1M0) for part B of the study
• Priority for study entry will be given to patients with easily accessible tumor and who consent to repeat biopsy; study entry will not be restricted to patients who agree to further biopsies; if a patient enrolls on study and later refuses biopsy (excluding diagnostic), he/she may remain on study
• Patients with operable or inoperable tumors will be eligible
• No prior therapy for the tumor, including chemotherapy, radiation therapy, immunotherapy, EGFR targeted therapies, or any other investigational agents
• Prior malignancies of sites other than the head and neck are allowed if disease free interval \>= 3 years; basal cell carcinomas of the skin and in situ cervical dysphagias are allowed within this three year interval if completely resected
• Documentation of evaluable tumor less than or equal to four weeks before treatment start
• ECOG performance status = 0, 1 or 2 (Karnofsky \>= 60%)
• Life expectancy of greater than or equal to 6 months
• Leukocytes \>= 3,000
• Absolute neutrophil count \>= 1,500
• Platelets \>= 100,000
• Total bilirubin within normal institutional limits unless due to hemolysis or Gilbert's syndrome

You may not qualify if:

• Patients with known brain involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 or other agents used in study
• Major surgery or significant traumatic injury occurring within 28 days prior to treatment
• Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjögren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
• Gastrointestinal tract disease resulting in an inability to take oral or enteral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, untreated or new cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because OSI-774 is an epidermal growth factor inhibitor with the potential for teratogenic or abortifacient effects based on the data suggesting that EGFR expression is important for normal organ development; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OSI-774, breastfeeding should be discontinued if the mother is treated with OSI-774
• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with OSI-774; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
• Patients on Coumadin are excluded from the study because of reports of interactions between the study drug and Coumadin

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Erlotinib Hydrochloride; Cisplatin; Radiotherapy, Intensity-Modulated

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Maura Gillison

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2002
• First Posted: January 27, 2003
• Study Start: October 1, 2002
• Primary Completion: July 1, 2007
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

US (1)