Comparison of Biomarker Modulation by Inhibition of EGFR and/or SRC Family

NCT00779389 | Completed Phase 1

• 1 other identifier: 07-124
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

The central hypothesis to be tested in this study is that dual blockade of EGFR and Src pathways or proteins are distinct compared to inhibition of either kinase alone in head and neck and lung cancers.

Conditions

Head and Neck Cancer; Non Small Cell Lung Cancer

Keywords

Head and Neck cancer

Outcome Measures

Primary Outcomes (1)

• The primary endpoints are comprised of a panel of tumor proteins to be obtained before after administration of the study drugs.

  2-3 week preoperative period of drug administration

Study Arms (4)

Arm A

EXPERIMENTAL

Erlotinib 150 mg

Drug: Erlotinib

Arm B

EXPERIMENTAL

Dasatinib + placebo

Drug: Dasatinib + Placebo

Arm C

EXPERIMENTAL

Erlotinib (150 mg) plus Dasatinib (100 mg) for 14-21 days.

Drug: Erlotinib plus Dasatinib

Arm D

PLACEBO COMPARATOR

Placebo for 14-21 days

Drug: Placebo

Interventions

Erlotinib DRUG

Erlotinib 150mg will be taken once a day for 14-21days.

Also known as: Tarceva

Arm A

Dasatinib + Placebo DRUG

Dasatinib (100 mg) once a day for 14-21 days.

Also known as: Sprycel

Arm B

Erlotinib plus Dasatinib DRUG

Erlotinib (150 mg PO qD) plus Dasatinib (100 mg PO qD) 14-21 days

Also known as: Tarceva and Sprycel

Arm C

Placebo DRUG

Placebo for 14-21 days.

Arm D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed, head and neck or lung cancers
• Any NSCLC histology is eligible. Stages I, II, IIIA (T3N1 only) or recurrent NSCLC that will be managed with surgery are eligible.
• Primary tumors of any head and neck (oral cavity, oropharynx, hypopharynx, or larynx) or lung site will be included.
• Surgical resection of head and neck or lung must be planned, either as primary treatment or salvage. Patients must have tissue available prior to receiving drug(s).
• Age greater then 18 years.
• ECOG performance status 0-2.
• Women of childbearing potential (WOCBP) must have:
• A negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration
• Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped.
• Ability to take oral medication (dasatinib must be swallowed whole).
• Concomitant Medications
• Patients agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib).
• Patient agrees that IV biphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
• Adequate hematologic, renal and hepatic function.
• Have signed written informed consent including a HIPPA form according to institutional guidelines.

You may not qualify if:

• Subjects who fail to meet the above criteria.
• Prior therapy for head and neck or lung cancers is allowed, with the exception of EGFR inhibitors. Any systemic therapy should have been completed at least 30 days prior to study enrollment.
• Pregnancy or breastfeeding. Women (patients or partners of male patients) of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy.
• Any unresolved chronic toxicity grade greater or equal to 2 from previous anticancer therapy (except alopecia and anemia).
• Acute hepatitis, known HIV, or active uncontrolled infection.
• Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.
• Prior treatment with an EGFR inhibitor (tyrosine kinase inhibitor).
• History of thromboembolic event or other condition currently requiring anticoagulation with warfarin (Coumadin). Patients whose therapy is changed to heparin is eligible.
• History of any other cancer except basal cell carcinoma of the skin.
• Concurrent medical condition which may increase the risk of toxicity, including:
• \* Pleural or pericardial effusion of any grade
• History of significant bleeding disorder unrelated to cancer, including:
• Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease).
• Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
• Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (3)

• Bauman JE, Duvvuri U, Gooding WE, Rath TJ, Gross ND, Song J, Jimeno A, Yarbrough WG, Johnson FM, Wang L, Chiosea S, Sen M, Kass J, Johnson JT, Ferris RL, Kim S, Hirsch FR, Ellison K, Flaherty JT, Mills GB, Grandis JR. Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer. JCI Insight. 2017 Mar 23;2(6):e90449. doi: 10.1172/jci.insight.90449.

  PMID: 28352657 DERIVED

• Van Allen EM, Lui VW, Egloff AM, Goetz EM, Li H, Johnson JT, Duvvuri U, Bauman JE, Stransky N, Zeng Y, Gilbert BR, Pendleton KP, Wang L, Chiosea S, Sougnez C, Wagle N, Zhang F, Du Y, Close D, Johnston PA, McKenna A, Carter SL, Golub TR, Getz G, Mills GB, Garraway LA, Grandis JR. Genomic Correlate of Exceptional Erlotinib Response in Head and Neck Squamous Cell Carcinoma. JAMA Oncol. 2015 May;1(2):238-44. doi: 10.1001/jamaoncol.2015.34.

  PMID: 26181029 DERIVED

• Gross ND, Bauman JE, Gooding WE, Denq W, Thomas SM, Wang L, Chiosea S, Hood BL, Flint MS, Sun M, Conrads TP, Ferris RL, Johnson JT, Kim S, Argiris A, Wirth L, Nikiforova MN, Siegfried JM, Grandis JR. Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer. Clin Cancer Res. 2014 Jun 15;20(12):3289-98. doi: 10.1158/1078-0432.CCR-13-3360. Epub 2014 Apr 11.

  PMID: 24727329 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Dasatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Pyrimidines

Study Officials

• Jennifer R Grandis, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2008
• First Posted: October 24, 2008
• Study Start: January 1, 2009
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: January 13, 2016

Record last verified: 2015-02

Locations

US (1)