Know Cancer

forgot password

Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)

Phase 1/Phase 2
18 Years
Open (Enrolling)
Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)



- Determine the safety and feasibility of erlotinib hydrochloride and cetuximab in
patients with advanced solid tumors. (Phase I)

- Determine the efficacy of this regimen, in terms of objective tumor response rate, in
patients with advanced non-small cell lung cancer (NSCLC) pre-treated with platinum.
(Phase II)


- Determine the maximum tolerated dose of this regimen in these patients. (Phase I)

- Determine the efficacy of this regimen, in terms of response rate, in these patients.
(Phase I)

- Determine the progression-free and overall survival of patients treated with this
regimen. (Phase II)

- Determine the frequency and severity of toxicities of this regimen in these patients.
(Phase II)

- Determine epidermal growth factor receptor (EGFR) and K-RAS mutation status. (Phase II)

- Evaluate EGFR protein expression and protein expression of downstream markers (e.g.,
pMAPK, pAKT, p27, and Ki-67). (Phase II)

- Evaluate the levels of marker proteins (e.g., pMAPK, pAKT, p27, and Ki-67) in buccal
cells. (Phase II)

- Determine gene copy number by EGFR fluorescent in situ hybridization (FISH). (Phase II)

- Identify EGFR polymorphisms by analysis of genomic DNA from peripheral blood
mononuclear cells. (Phase II)

- Determine if the continued presence or absence of mutant K-RAS tumor DNA correlates
with response and/or outcome. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by an open-label, phase II study.

- Phase I: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and
cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days
in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride and cetuximab
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which ≥ 2 of 6 patients experience dose-limiting toxicity. At least 6
patients are treated at the MTD.

- Phase II: Patients receive erlotinib hydrochloride and cetuximab at the MTD determined
in phase I.

Blood and buccal samples are acquired from patients at baseline and prior to courses 2 and
3. Samples are examined by fluorescent in situ hybridization (FISH), immunohistochemistry,
polymorphism analysis, and protein expression assays to assess molecular markers (epidermal
growth factor receptor, K-RAS, pMAPK, pAKT, p27 and Ki-67) for biologic effects and
predictive response.

After completion of phase I treatment, patients are followed for 30 days or until all
toxicities resolve. After completion of phase II treatment, patients are followed

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study

Inclusion Criteria

Inclusion criteria

- For the phase I portion of the study (completed 10/05/08), patients must have
cytologically or histologically proven advanced solid tumors for which there is no
standard effective therapy available.

- Any number of prior chemotherapy regimens are allowed for the both the Phase I and
Phase II portions

- For the phase II portion patients must have cytologically or histologically proven
selected stage IIIB (pleural effusion) or IV NSCLC. Patients with NSCLC that have
progressed or recurred after first-line therapy for stage IIIA or IIIB may also be

- Patients must have measurable disease by RECIST criteria for the Phase II portion.
Disease in previously irradiated sites is considered measurable if there is clear
disease progression following radiation therapy. Patients with evaluable disease
(bone metastases, pleural fluid, ascites, etc.) may be included in the phase I
portion of the trial (completed 10/08/08).

- Must be 18 years of age or older.

- Patients must have a performance status of 0 -2.

- Patients must have an estimated survival of at least 3 months.

- Any prior chemotherapy must have been completed at least 4 weeks prior to start of
treatment. For prior mitomycin chemotherapy a 6-week interval is required. Prior
radiation must have been completed at least 2 weeks prior to start of therapy.
Patients must have recovered from acute reversible medically significant side effects
of prior chemotherapy regimens or radiotherapy to NCI-CTC < grade 1 (excluding
alopecia). Prior herceptin is allowed.

- Patients must have adequate renal function as documented by a serum creatinine < 1.5
mg/dl or a calculated creatinine clearance of > 45 ml/min (see protocol Appendix D
for formula for calculating creatinine clearance).

- Patients must have adequate liver function as documented by serum bilirubin < 1.5 x
ULN. AST must be < 2.5 x institutional upper limit of normal.

- Patients must have a pretreatment granulocyte count of >1500/mm3 and platelet count
of >100 000/mm3.

- Patients with asymptomatic treated brain metastasis (surgical resection or
radiotherapy) may be included if they are neurologically stable and have been off
steroids and anticonvulsants for at least 2 weeks.

- All patients must give voluntary written informed consent.

- Patients must be able to take and retain oral medication.

- Documentation of a negative serum pregnancy test.

- Patients on coumadin should have their INR monitored at least once per week or more
frequently depending on the investigator's judgment. There have been some case
reports of increased INR when coumadin is co-administered with erlotinib.

Exclusion criteria

- Patients who have received erlotinib, cetuximab, or any other EGFR-directed therapy
(excluding herceptin).

- Patients with symptomatic brain metastasis or still requiring steroids and
anti-convulsants may not be included.

- For the phase II portion of the study, no other prior malignancy is allowed except
for the following: adequately treated basal cell or squamous cell skin cancer, in
situ cervical cancer, adequately treated stage I or II cancer from which the patient
is currently in complete remission, and any other cancer from which the patient has
been disease-free for over five years

- Patients with acute hepatitis or known HIV.

- Patients with active or uncontrolled infection.

- Patients with significant history of uncontrolled cardiac disease; i.e., uncontrolled
hypertension, unstable angina, recent myocardial infarction (within prior 6 months),
uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection

- Patients with prior severe infusion reaction to a monoclonal antibody.

- Any concurrent chemotherapy not indicated in the study protocol or any other
investigational agent(s).

- Pregnant or breastfeeding females as the effects of these drugs on the unborn fetus
are unknown.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

Toxicity will be evaluated based on the standard NCI CTCAE V.3.0 grading criteria.

Outcome Time Frame:

Toxicity will be assessed on day 8, 15, 22 and subsequently at the beginning of every cycle.

Safety Issue:


Principal Investigator

David R. Gandara, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, Davis


United States: Food and Drug Administration

Study ID:




Start Date:

August 2006

Completion Date:

June 2014

Related Keywords:

  • Lung Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • stage IIIA non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • stage IV non-small cell lung cancer
  • recurrent non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasms



University of California Davis Cancer Center Sacramento, California  95817