MDACC Study Summary 2007-0638

Study Summary
No. 2007-0638:.......Advanced Cancers......Jennifer J. Wheler......Investigational Cancer Therapeutics

Study Summary Title



Study Summary Number:	2007-0638

Study Title:	An Umbrella Protocol for Histology-Independent, Phase I Modular Study Based on EGFR Mutation Status: Using Erlotinib Alone or in Combination with Cetuximab, Bortezomib, or Dasatinib to Overcome Resistance

Physician

New Patient Referral



Name:	Jennifer J. Wheler	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Investigational Cancer Therapeutics	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-563-1930 Contact us about clinical trials

General Information



Disease Group:	Advanced Cancers	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	Patients will have to return to MDACC approx 3 times during the course of Cycle 1 (including screening and end-of-study visits).

Treatment Agents:	Bortezomib Cetuximab Dasatinib Erlotinib	Home Care:	The initial dose of Erlotinib will be given in the clinic. Subsequent doses can be administered at home if no study visit is required by the protocol. Premedications, if necessary, may also be given at home.

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	N/A

Description/
Intervention:

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.

Study Objectives / Outcomes

Primary Objectives:

I. Determine reasonable dose of combination treatments, including Maximum Tolerated Dose (MTD) and toxicity profiles, via a brief initial "run-in"/dose escalation.

II. Evaluate response in patients with tumors that demonstrate EGFR-sensitive mutations, to treatment with single-agent erlotinib

III. Evaluate response in patients with tumors that demonstrate EGFR-resistant mutations, or patients who have previously demonstrated a response to EGFR inhibitors with subsequent resistance, to treatment with erlotinib combinations.

Secondary Objectives:

I. Correlate responses to treatment to the type of EGFR mutation and to the presence of other signaling aberrations.

II. Perform correlative studies including EGFR FISH analysis and Reverse Phase Protein Array (RPPA) to further elucidate molecular response and associations.

Study Status Information



Study Activation / Registration Date:	04/30/2009

IRB Review and Approval Date:	04/30/2009

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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.

Links

Registration Number: NCT00903734
Study Information on Clinical Trials Registry (clinicaltrials.gov)