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A Phase I Study of OSI-774 in Combination With Standard Fractionation Radiation Therapy in Patients With Oral Cavity or Oropharyngeal Cancer Stage II or III and in Combination With Standard Fractionation Radiation Therapy and Low Dose Daily Cisplatin in Patients With Oral Cavity or Oropharyngeal Cancer Stage III and IV


Phase 1
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

A Phase I Study of OSI-774 in Combination With Standard Fractionation Radiation Therapy in Patients With Oral Cavity or Oropharyngeal Cancer Stage II or III and in Combination With Standard Fractionation Radiation Therapy and Low Dose Daily Cisplatin in Patients With Oral Cavity or Oropharyngeal Cancer Stage III and IV


PRIMARY OBJECTIVES:

I. Determination of the maximally tolerated dose (MTD) of the combination of daily oral
OSI-774 and standard fractionation external beam radiation therapy in patients with oral
cavity (OC) or oropharyngeal (OP) squamous cell carcinoma (SCC), stage II and III.

II. Determination of the MTD of daily oral OSI-774, low dose daily cisplatin at 6 mg/m^2/day
and standard fractionation external beam radiation therapy in patients with oral cavity or
oropharyngeal SCC stage III and IV.

III. Determination of the safety of chronic oral dosing of OSI-774 after radiation therapy.

SECONDARY OBJECTIVES:

I. Determination of biological markers of activity of OSI-774 in tumor biopsy specimens from
patients with SCC of OC and OP pre and post therapy.

II. Determination of the ability of (18F)-FDG-PET scan to demonstrate biological activity of
OSI-774 in previously untreated patients with SCC of the OC and OP and to predict for
clinical response.

OUTLINE: This is a multicenter, dose-escalation study of erlotinib. Patients are assigned to
1 of 2 regimens according to disease stage.

Regimen A (patients with stage II [T2, N0] or III [T1-2, N1] disease): Patients receive oral
erlotinib once daily. Beginning on day 15, patients also undergo intensity-modulated
radiotherapy (IMRT) once daily 5 days a week for 7 weeks.

Regimen B (patients with stage III [T3, N0-1] or IV [T1-4, N2-3, M0 or T4, N0-1, M0]
disease): 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
maximum tolerated dose (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.

Patients are followed at 30 days and then every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 24-48 patients (12-24 per regimen) will be accrued for this
study within 6-24 months.


Inclusion Criteria:



- 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

- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- APTT/INR within normal institutional limits; patients who have abnormalities in
APTT/INR that are correctable after administration of vitamin K are eligible

- No uncontrolled diabetes mellitus as glucose must be within a consistently normal
range for each patient in order to standardize PET scan interpretations

- No known malabsorption syndrome

- G-tube dependent patients are eligible

- The effects of OSI-774 on the developing human fetus at the recommended therapeutic
dose are unknown; for this reason, women of child-bearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control) for
the duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

Summarized using descriptive statistics.

Outcome Time Frame:

Up to 7 weeks

Safety Issue:

Yes

Principal Investigator

Maura Gillison

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03155

NCT ID:

NCT00049166

Start Date:

October 2002

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Oropharyngeal Neoplasms

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205