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An Umbrella Protocol for Histology-Independent, Phase I Modular Study Based on Epidermal Growth Factor Receptor (EGFR) Mutation Status: Using Erlotinib Alone or in Combination With Cetuximab, Bortezomib, or Dasatinib to Overcome Resistance

Phase 1
18 Years
Open (Enrolling)
Advanced Cancers

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Trial Information

An Umbrella Protocol for Histology-Independent, Phase I Modular Study Based on Epidermal Growth Factor Receptor (EGFR) Mutation Status: Using Erlotinib Alone or in Combination With Cetuximab, Bortezomib, or Dasatinib to Overcome Resistance

Drug Administration and Study visits for Erlotinib hydrochloride:

If you will be taking Erlotinib hydrochloride in this study, you will take Erlotinib
hydrochloride by mouth daily at least 1 hour before eating and 2 hours after eating. You
will have study visits once a month. If you continue to be on study longer than 2 cycles,
study visits may become less frequent.

At these visits, the following tests and procedures will be performed:

- Your performance status will be recorded.

- You will be asked to list any drugs you may be taking, including over-the-counter

- You will be asked about any symptoms you may have.

- You will have a physical exam, including measurement of your vital signs.

- Blood (about 2 teaspoons) will be collected for routine tests

After the first 8 weeks on study, you will have a CT or MRI scan to check the status of the
disease. You will have a CT or MRI scan every 8 to 12 weeks after that.

You may continue taking Erlotinib hydrochloride for as long as you are benefitting. You
will be taken off study if the disease gets worse or intolerable side effects occur. If the
disease gets worse, the study doctor may assign you to 1 of 3 studies. The study doctor
will discuss this in more detail with you.

Length of Study:

Your participation on this screening study will be over after all of the screening tests and
procedures described above have been completed.

This is an investigational study. Up to 102 participants will take part in this study. All
will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with pathologically confirmed advanced or metastatic cancer that is
refractory to standard therapy, relapsed after standard therapy, or who have had no
standard therapy that induces a CR rate of at least 10% or improves survival by at
least three months.

2. Patients must have tumor tissue available, either from an archival specimen, or from
a recent biopsy, to be analyzed for EGFR mutation. Patients must sign consent for the
umbrella protocol prior testing for EGFR mutation. Patients will be eligible if they
have an EGFR-sensitive mutation, OR if they have an EGFR-resistant mutation, OR if
they do not have an EGFR mutation, but have benefited from EGFR inhibitor therapy
(including either >/= 4 months of stable disease [SD] OR a >/= partial response

3. Measurable or non-measurable disease.

4. Patients must be >/= 6 wks beyond treatment with a nitrosourea or mitomycin-C, >/= 4
wks beyond other chemotherapy or XRT, and must have recovered to for any treatment-limiting toxicity resulting from prior therapy. (Exception:
patients may have received palliative low dose XRT one week before treatment provided
it is not given to the only targeted lesions).

5. (continued from above) Also, patients who have received non-chemotherapeutic
biological agents will need to wait at least 5 half-lives or 4 wks, whichever is
shorter, from the last day of treatment.

6. ECOG performance status /= 60%)

7. Patients must have normal organ and marrow function defined as: absolute neutrophil
count >/=1,000/mL; platelets >/=50,000/mL; creatinine bilirubin
8. Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 30 days after the last dose.

9. Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

1. Patients with uncontrolled concurrent illness, including but not limited to: ongoing
or active infection; altered mental status or psychiatric illness/social situations
that would limit compliance with study requirements and/or obscure study results.

2. Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg,
diastolic blood pressure > 90 mm Hg on medication).

3. Patients with clinically significant cardiovascular disease: history of CVA within 6
months, myocardial infarction or unstable angina within 6 months, or unstable angina

4. Patients with colorectal carcinoma with tumors that demonstrate a KRAS mutation.

5. Pregnant or lactating women

6. Patients with a history of bone marrow transplant within the previous two years

7. Patients with a known hypersensitivity to any of the components of the drug products.

8. Patients who will be on treatment arm consisting of erlotinib and dasatinib should
not be taking any drugs that are potent inhibitors or inducers of CYP34A

9. Patients unable to swallow oral medications or with pre-existing gastrointestinal
disorders that might interfere with proper absorption of oral drugs.

10. Patients with major surgery within 30 days prior to entering the study.

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated Dose (MTD) and toxicity profiles via a brief initial "run-in"/dose escalation.

Outcome Time Frame:

Continous reassessment during dose level/cycles (28 days)

Safety Issue:


Principal Investigator

Jennifer Wheler, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

May 2009

Completion Date:

Related Keywords:

  • Advanced Cancers
  • Metastatic Cancer
  • Histology-independent
  • EGFR Mutation
  • EGFR inhibitor-sensitive mutation
  • Erlotinib Hydrochloride
  • Tarceva
  • OSI-774
  • Cetuximab
  • Bortezomib
  • Dasatinib
  • Neoplasms



UT MD Anderson Cancer Center Houston, Texas  77030