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Erlotinib and Cetuximab in Treating Patients With Advanced Solid Tumors With Emphasis on Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT00408499
Recruitment Status : Completed
First Posted : December 7, 2006
Results First Posted : May 8, 2017
Last Update Posted : May 8, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of California, Davis

Tracking Information
First Submitted Date  ICMJE December 6, 2006
First Posted Date  ICMJE December 7, 2006
Results First Submitted Date  ICMJE January 19, 2017
Results First Posted Date  ICMJE May 8, 2017
Last Update Posted Date May 8, 2017
Study Start Date  ICMJE August 2006
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
  • Number of Patients Experiencing a DLT [ Time Frame: baseline through cycle 1 of treatment ]
    Patients will be followed during cycle 1 for the occurrence of a protocol defined dose limiting toxicity
  • Number of Patients Correlated With Best Overall Response. [ Time Frame: Every two cycles from first dose to last dose of study drugs ]
    To determine the efficacy, as measured by objective tumor response rate (RICIST criteria), of daily oral erlotinib and weekly intravenous cetuximab in patients with advanced NSCLC. Best overall response per patient will be reported below.
Original Primary Outcome Measures  ICMJE
 (submitted: December 6, 2006)
  • Toxicity
  • Response rate
  • Objective status as measured by complete, non-complete, and partial response, progressive and stable disease
  • Best response
Change History Complete list of historical versions of study NCT00408499 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
Patient Outcome [ Time Frame: Patients will be followed until death ]
In the Phase II portion of the study, patients will be followed for both disease free progression by capturing disease progression date and for over all survival by capturing death date.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2006)
  • Assessment of molecular markers for biologic effects and predictive response
  • Overall survival
  • Progression-free survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Erlotinib and Cetuximab in Treating Patients With Advanced Solid Tumors With Emphasis on Non-Small Cell Lung Cancer
Official Title  ICMJE Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)
Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving erlotinib together with cetuximab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib and cetuximab and to see how well they work in treating patients with advanced solid tumors or progressive or recurrent stage III or stage IV non-small cell lung cancer.

Detailed Description

OBJECTIVES:

Primary

  • 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)

Secondary

  • 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 periodically.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lung Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: cetuximab
    Cetuximab will be administered intravenously weekly at the maximum tolerated dose (determined in Phase I portion of the study) on a 28 day cycle. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy.
    Other Name: Erbitux
  • Drug: erlotinib
    Erlotinib will be taken by mouth daily on a 28 day cycle. It is in tablet form. The dose will be determined in Phase I portion of the study. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy.
    Other Name: Tarceva
Study Arms  ICMJE Experimental: Erlotinib + Cetuximab
Daily erlotinib combined with weekly cetuximab
Interventions:
  • Drug: cetuximab
  • Drug: erlotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 8, 2012)
64
Original Enrollment  ICMJE
 (submitted: December 6, 2006)
62
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 considered.
  • 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 fraction.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00408499
Other Study ID Numbers  ICMJE CDR0000517090
P30CA093373 ( U.S. NIH Grant/Contract )
UCDCC-177 ( Other Identifier: University of California Davis )
BMS-4608 ( Other Identifier: Bristol Myers Squibb )
BMS-CA225-261 ( Other Identifier: Bristol Myers Squibb )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, Davis
Study Sponsor  ICMJE University of California, Davis
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: David R. Gandara, MD University of California, Davis
PRS Account University of California, Davis
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP