A Study of Dasatinib, Cetuximab and Radiation With or Without Cisplatin in HNSCC

NCT00882583 | Terminated Phase 1 Results DMC

• 2 other identifiers: J08101CA180123
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objective for Phase I

1. 1.To determine the maximally tolerated dose (MTD) of daily Oral dasatinib in combination with cetuximab/RT in Cohort A.
2. 2.To determine the MTD of daily oral dasatinib in combination with cisplatin/cetuximab/RT in Cohort B

Conditions

Head and Neck Cancer

Keywords

HNSCC; Dasatinib; Cetuximab; Cisplatin

Outcome Measures

Primary Outcomes (1)

• MTD of Daily Oral Dasatinib in Combination With Cetuximab/RT in Cohort A and Daily Oral Dasatinib in Combination With Cetuximab/Cis or Carboplatin/RT in Cohort B 2. MTD of Daily Oral Dasatinib in Combination With Cisplatin/Cetuximab/RT in Cohort B

  The Maximum Tolerated Dose (MTD) for Dasatinib was defined as a) the dose producing DLT ( Dose limiting toxicity) in 0-1 out of 6 patients, or b) the dose level below the dose which produced DLT in \<2 out of 6 patients, or c) the dose of 150mg PO QD with less than 33% rate of DLT.

  Last day of Radiation

Study Arms (2)

Dasatinib/Cetuximab/RT

EXPERIMENTAL

In Cohort A , there will be an initial "run-in period" of single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8 and oral dasatinib at specific dose level from day 8-14. Cohort A will consist of patients with AJCC stage II (T2N0) and III (T1-2N1) SCCHN of oral cavity, oropharynx, T2N0 hypopharynx, T2N0-1 supraglottic larynx. Treatment will be dasatinib at specific dose level in combination with cetuximab 250mg/m2 IV and radiation therapy (RT) 70Gy at 2Gy/fn.

Drug: Cetuximab; Drug: Dasatinib; Radiation: Radiation Therapy

Dasatinib/Cetuximab/cisplatin/RT

EXPERIMENTAL

In Cohort B, there will be an initial "run-in period" of single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8 and oral dasatinib at specific dose level from day 8-14. Cohort B will include patients with AJCC stage III (T3N0-1) and IV (T1-4N2-3M0, T4N0-1M0) squamous cell carcinoma of Oral Cavity, Oropharynx, Hypopharynx, and Larynx. Treatment will be daily dasatinib at specific dose level, in combination with q 3 week cisplatin 75mg/m2, weekly cetuximab 250mg/m2 IV and RT 70Gy ( 2gy per fraction).

Drug: Cetuximab; Drug: Dasatinib; Drug: Cisplatin; Radiation: Radiation Therapy

Interventions

Cetuximab DRUG

single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8

Also known as: Erbitux

Dasatinib/Cetuximab/RT; Dasatinib/Cetuximab/cisplatin/RT

Dasatinib DRUG

Oral Dasatinib Days 8 through 64.

Also known as: Sprycel, BMS-354825

Dasatinib/Cetuximab/RT; Dasatinib/Cetuximab/cisplatin/RT

Cisplatin DRUG

Q 3 weeks (Days 15, 36 and 57): +/- 3 Days

Also known as: Cisplatinum, cis-diamminedichloroplatinum(II) (CDDP), Platinol, Platin

Dasatinib/Cetuximab/cisplatin/RT

Radiation Therapy RADIATION

Standard Radiation Therapy.

Dasatinib/Cetuximab/RT; Dasatinib/Cetuximab/cisplatin/RT

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically confirmed operable or inoperable squamous cell carcinoma of OC, OP, HP, or larynx prior to proceeding with treatment.
• Patients must be AJCC stage II (T2N0) or III (T1-2N1) of oral cavity, oropharynx, only T2N0 of hypopharynx, T2N0-1 supraglottic laryngeal cancers (AJCC Fifth Edition, 1997) for Arm A of the study, and must be AJCC stage III (T3N0-1) or IV (T1-4N2-3M0, T4N0-1M0) oral cavity, oropharynx, hypopharynx, glottic and supraglottic laryngeal cancers for Arm B of the study.
• Patients must have measurable disease,.
• Subject, age ≥ 18 years.
• Performance Status (ECOG) 0-1
• No previous therapy for the tumor, including chemotherapy, radiation therapy, immunotherapy, EGFR targeted therapy, src directed therapies or investigational agents.
• Adequate Organ Function.
• Total bilirubin ≤ 1.5 x ULN
• AST and ALT ≤ 2.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• Hepatic enzymes (AST, ALT) ≤ 2.5 times the institutional ULN.
• Serum Na, K+, Mg2+, Phosphate and Ca2+ ≥ lower limit of normal (LLN).
• Serum Creatinine clearance ≥ 60 ml/min.
• Hemoglobin, neutrophil count, platelets, PT, PTT all Grade 0-1.
• ANC ≥ 1,500/mL

You may not qualify if:

• Any prior radiation above the clavicles
• Prior head and neck cancer. Any other prior invasive malignancy if disease free interval is ≤ 3 years. Nonmelanomatous carcinomas of the skin and in situ cervical dysplasia are allowed if completely resected within three year interval or can be completely resected prior to starting treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab, dasatinib or other agents used in study.
• Gastrointestinal tract disease resulting in an inability to take or absorb oral or enteral medication.
• Concurrent medical condition which may increase the risk of toxicity, including:
• Pleural or pericardial effusion of any grade.
• Uncontrolled angina, congestive heart failure or MI within (6 months).
• Diagnosed congenital long QT syndrome.
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
• Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec).
• Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to protocol treatment.
• 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

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; Dasatinib; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Results Point of Contact

• Title: Shanthi Marur
• Organization: FDA

shanthi.marur@fda.hhs.gov

2404026373

Study Officials

• Shanthi Marur, MD

  Johns Hopkins Universtiy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2009
• First Posted: April 16, 2009
• Study Start: July 1, 2009
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: January 9, 2019
• Results First Posted: February 23, 2017

Record last verified: 2019-01

Locations

US (2)