Trial Outcomes & Findings for A Dose Finding Study of Eribulin Mesylate and Cetuximab For Patients With Advanced Head and Neck and Colon Cancer (NCT NCT01744340)

Last Updated: 2020-02-17

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

23 participants

Primary outcome timeframe

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

Results posted on

2020-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Head and Neck Cetuximab, 400 mg/m2 cycle 1 week 1, then 250 mg/m2/weekly there after Eribulin Mesylate 1.4mg/m2 Head and neck: 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	Colon- Closed as of May 2014 Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle Colon- Closed as of May 2014: Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle
Overall Study STARTED	8	15
Overall Study COMPLETED	8	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Head and Neck n=8 Participants Cetuximab, 400 mg/m2 cycle 1 week 1, then 250 mg/m2/weekly there after Eribulin Mesylate 1.4mg/m2 Head and neck: 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	Colon- Closed as of May 2014 n=15 Participants Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle Colon- Closed as of May 2014: Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	58.5 years n=5 Participants	71 years n=7 Participants	60.6 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	15 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

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

Population: Outcome measure that address the dose of 1.4 mg/m2,6 patients were treated (1 head and neck 5 colon). 12 patients were enrolled in the course of the MTD dose finding,10 colon and 2 head and neck. All other results sections are inclusive of all patients(dose finding +expansion cohort).

Outcome measures

Outcome measures
Measure	Head and Neck n=1 Participants Cetuximab, 400 mg/m2 cycle 1 week 1, then 250 mg/m2/weekly there after Eribulin Mesylate 1.4mg/m2 Head and neck: 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	Colon- Closed as of May 2014 n=5 Participants Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle Colon- Closed as of May 2014: Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle
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.	0 participants	0 participants

SECONDARY outcome

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

This shows patients able to achieve Stable disease or better as their best response during course of study participation. Response will be evaluated by Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline v1.1 RECIST Guideline version 1.1 Response Criteria Complete Response:Disappearance of all target lesions; Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease:At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease:Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study

Outcome measures

Outcome measures
Measure	Head and Neck n=8 Participants Cetuximab, 400 mg/m2 cycle 1 week 1, then 250 mg/m2/weekly there after Eribulin Mesylate 1.4mg/m2 Head and neck: 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	Colon- Closed as of May 2014 n=15 Participants Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle Colon- Closed as of May 2014: Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle
Response Rate (Whether Patient's Disease is Progressing or Being Controlled) of Patients With Head and Neck Cancer Treated With Eribulin Mesylate and Cetuximab.	6 participants	2 participants

Adverse Events

Head and Neck

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

Colon- Closed as of May 2014

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Head and Neck n=8 participants at risk Cetuximab, 400 mg/m2 cycle 1 week 1, then 250 mg/m2/weekly there after Eribulin Mesylate 1.4mg/m2 Head and neck: 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	Colon- Closed as of May 2014 n=15 participants at risk Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle Colon- Closed as of May 2014: Eribulin Mesylate: 1.4 mg/m2 IV infusion days 1 and 8 of 21 day cycle
Investigations S b(4), pleural effusion(4), Dyspnea(4), asp(4), lung inf (4), resp acidosis(4)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Acute respiratory failure (5)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Dyspnea(2), K(3) , MG(2) , ANC(3), Nausea(2), Vomitting(2)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Edema(3), dysphyagia(3), hemolytic Anemia(3), PLT(4), calcium(1),WBC(1) , lymph(3)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Hemorragic shock(5), HGB/Anemia(3), Chloride(1) , CO2(1) , AST(2), ALT(2) , PT(1)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations COPDdyspnea(2),neutr(3),sepsis(4),anemia(2),Leuk(3),Lymph (3), Hypergly(2),Hypoca(2), Hypokal(1)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Dyspnea(1), Sepsis(4), Anemia(2), Lymphocyte decrease (3), Hypocalcemia(2)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Feb neut(3), neut(4),anemia(3), leuk(3),hypona(3), lymph(3) , CR(1), Ca(2), K(1), Gluc(1), MG(2)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Feb Neut(res).Neut(0),An(1),Leuk(0),Hypona(1),Lymph(1),CR(0),Ca(1),K(0),Gluc(0),MG(1),URI(2)O Muc(3)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Respiratory Infection (5)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Dyspnea(2), Febrile Neutropenia(3)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Dyspnea(2), Productive cough(2), Wheezing(3)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Dys(1),PrCo(0),Whez(0),Resp(4),An(3),HGB(3),Leuk(1),Lymph(3),ALB(2),CA(2),K(3),MG(2),PHOS(4),GLU(2)	12.5% 1/8 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	0.00% 0/15 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.
Investigations Na(3), confusion(1), Fatigue(3), constipation(2), anorexia(3)	0.00% 0/8 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.	6.7% 1/15 • Number of events 1 • Adverse events were collected pre-study, within 72 hours of day 1 if each cycle, at day 8 of each cycle, at end of treatment visit and 30 days post last dose of drug.

Other adverse events

Additional Information

Howard Safran, MD

BrUOG-Brown University Oncology Research Group

Phone: 4018633000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place