A Dose Finding Study of Eribulin Mesylate and Cetuximab For Patients With Advanced Head and Neck and Colon Cancer

NCT01744340 | Completed Phase 1 Results DMC

• 1 other identifier: BrUOG 254
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine if the full dose of eribulin mesylate can be safely given with the full dose of cetuximab. The activity of the combination of eribulin mesylate and cetuximab on recurrent head and neck cancer and colon cancer will also be assessed.

Conditions

Head and Neck Cancer; Colon Cancer

Keywords

Head and Neck; Colon

Outcome Measures

Primary Outcomes (1)

• If Eribulin Mesylate, up to a Maximum Dose of 1.4 mg/m2 Day 1 and 8 of a 21 Day Cycle, Can be Safely Combined With Full Dose Cetuximab for Patients With Advanced Head and Neck Cancer and Colon Cancer.

  A DLT was defined as: * Grade 4 neutropenia (ANC \< 500/mm3) for \> 7 days * ANC \<1000/mm3 with fever or infection * Platelets \<25,000/mm3 * Platelets \<50,000/mm3 requiring transfusion * Grade 3 or grade 4 treatment related non-hematologic toxicities excluding alopecia. Grade 3 nausea, vomiting or diarrhea will only be considered a dose limiting toxicity if it occurs despite maximal medical support. Grade 3 or grade 4 hypomagnesemia will not be considered a dose limiting toxicity since it is an expected side effect of cetuximab and can be corrected. Other grade 3 or grade 4 electrolyte abnormalities will not be considered dose limiting toxicities if the electrolyte disorder can be corrected to grade 2 or less within 72 hours. * EGFR dermatologic toxicity should be graded according to the toxicity scale for EGFR associated reactions. The first episode of grade 3 or grade 4 rash will not be considered a DLT. * If any patient receives \< 70% of the planned dose of eribulin mesylat

  From Day 1 of Drug through end of cycle 2 equals (approximately) 42 days

Secondary Outcomes (1)

• Response Rate (Whether Patient's Disease is Progressing or Being Controlled) of Patients With Head and Neck Cancer Treated With Eribulin Mesylate and Cetuximab.

  From beginning of treatment to progression of disease, for an expected average of 1 year

Study Arms (2)

head and neck

EXPERIMENTAL

Cetuximab, 400 mg/m2 cycle 1 week 1, then 250 mg/m2/weekly there after Eribulin Mesylate 1.4mg/m2

Drug: Head and neck

Colon- closed as of May 2014

EXPERIMENTAL

Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle

Drug: Colon- Closed as of May 2014

Interventions

Head and neck DRUG

Eribulin mesylate is administered by IV infusion over 2-5 minutes on day 1 and 8 of a 21 day cycle 1.4mg/m2 and Cetuximab 400 mg/m2 cycle 1 week 1, then 250 mg/m2/weekly thereafter Dose Level 1: 0.7 mg/m2 IV infusion days 1 and 8 of 21 day cycle Dose Level 2: 1.0 mg/m2 IV infusion days 1 and 8 of 21 day cycle Dose Level 3: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle

head and neck

Colon- Closed as of May 2014 DRUG

Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle

Colon- closed as of May 2014

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 advanced squamous cell cancer of the head and neck with progression after at least one prior therapy. (Chemoradiation is considered one line of therapy). Patients with unknown Head and Neck primaries are also eligible
• In the dose escalation cohorts, patients with advanced colon adenocarcinoma with wild-type kras who have previously received at least two lines of therapy for advanced disease are eligible- No longer applicable post February 2013 as all patients have been enrolled to the dose escalation phase
• In the expansion phase for patients with advanced colorectal cancer, only patients with mutated kras who have previously received at least two lines of therapy for metastatic disease will be eligible. Pathology report from diagnosis and report documenting KRAS status to be sent to BrUOG. No longer applicable as this phase of the study has been closed as of 5/6/2014 secondary to the lack of efficacy and activity of the single agent.
• Life expectancy of at least 3 months
• Patients must be aged 18 years or older
• Patients with measurable tumors according to RECIST .
• Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• No severe concurrent illness that would interfere with protocol therapy.
• Patients must have adequate renal function as evidenced by ≤1.5 mg/dL or creatinine clearance \> 40 mL/minute (min).
• Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) \> 1.5 x 109/L and platelet count \> 100 x 109/L.
• Patients must have adequate hepatic function as evidenced by bilirubin ≤ 1.5 times the upper limit of normal (ULN) and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 x ULN (in the case of liver metastases ALT and AST ≤ 5 x ULN).
• Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or below, except for alopecia.
• Patients must be willing and able to comply with the study protocol for the duration of the study.
• Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
• No other active invasive malignancy unless disease free for at least 2 years.

You may not qualify if:

• For Head and Neck patients, no progression while receiving an EGFR inhibitor or within 6 months of stopping treatment with an EGFR inhibitor.
• Patients who received chemotherapy or investigational therapy within 3 weeks before treatment initiation. Radiation must be completed within 2 weeks before treatment initiation.
• Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
• Patients who participated in a prior eribulin mesylate clinical trial, whether or not they received eribulin mesylate.
• Patients with other significant disease or disorders that, in the investigator's opinion, would exclude the patient from the study.
• Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test; women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Peri-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks.
• Grade 2 or worse neuropathy.
• Significant cardiovascular impairment (history of congestive heart failure \> NYHA G II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia.
• QTc \> 500 msec

Sponsors & Collaborators

• howard safran: lead
• Fatima Memorial Hospital: collaborator
• Montefiore Medical Center: collaborator
• Rhode Island Hospital: collaborator
• The Miriam Hospital: collaborator

Study Sites (4)

Montefiore

The Bronx, New York, 10467, United States

Location

Memorial Hospital

Pawtucket, Rhode Island, 02860, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02904, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Colonic Neoplasms

Interventions

TNFAIP8 protein, human

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Howard Safran, MD
• Organization: BrUOG-Brown University Oncology Research Group

kristen_mitchell@brown.edu

4018633000

Study Officials

• Howard Safran, MD

  Brown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: February 23, 2012
• First Posted: December 6, 2012
• Study Start: May 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: July 1, 2015
• Last Updated: February 17, 2020
• Results First Posted: February 10, 2016

Record last verified: 2020-02

Locations

US (4)