An Umbrella, Modular Study Based on Epidermal Growth Factor Receptor (EGFR) Mutation Status

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00903734
First received: May 14, 2009
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

The goal of this screening portion of this clinical research study is to learn if you are eligible to take part in a clinical research study using Tarceva (erlotinib hydrochloride) and either Erbitux (cetuximab), Velcade (bortezomib), or Sprycel (dasatinib).

If the results of the screening portion of this clinical research study show that you are eligible to take part in one of the studies described above, the study drug that you will be assigned to take will depend on the results of biomarker analysis performed as a part of the screening tests described below. Biomarkers are chemical "markers" in the blood/tissue that may be related to how your body might react to the study drug.


Condition Intervention Phase
Advanced Cancers
Drug: Erlotinib Hydrochloride (Tarceva)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) and toxicity profiles via a brief initial "run-in"/dose escalation. [ Time Frame: Continous reassessment during dose level/cycles (28 days) ] [ Designated as safety issue: Yes ]
    MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle (induction phase). DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0, even if expected and believed related to the study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by the NCI-CTCAE), despite supportive care; any Grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE that is attributable to the therapy.


Estimated Enrollment: 102
Study Start Date: May 2009
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib Hydrochloride
Those eligible for umbrella of studies and have not received Erlotinib hydrochloride in past, will first receive Erlotinib hydrochloride alone.
Drug: Erlotinib Hydrochloride (Tarceva)
Dose of 150 mg daily by mouth.
Other Names:
  • Erlotinib
  • OSI-774

Detailed Description:

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 drugs.
  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 [PR]).
  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 </= Grade 1 toxicity 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 </= 2 (Karnofsky >/= 60%)
  7. Patients must have normal organ and marrow function defined as: absolute neutrophil count >/=1,000/mL; platelets >/=50,000/mL; creatinine </= 2 X ULN; total bilirubin </= 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 5 X ULN.
  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 document.

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 pectoris.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903734

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Jennifer Wheler, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00903734     History of Changes
Other Study ID Numbers: 2007-0638, NCI-2012-01633
Study First Received: May 14, 2009
Last Updated: June 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Metastatic Cancer
Histology-independent
EGFR Mutation
EGFR inhibitor-sensitive mutation
Erlotinib Hydrochloride
Tarceva
OSI-774
Cetuximab
Bortezomib
Dasatinib

Additional relevant MeSH terms:
Erlotinib
Mitogens
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Mitosis Modulators

ClinicalTrials.gov processed this record on October 19, 2014