Trial Outcomes & Findings for Cetuximab and/or Dasatinib in Patients With Colorectal Cancer and Liver Metastases That Can Be Removed by Surgery (NCT NCT00835679)

Results Overview

Patients who experienced a pre-to-post treatment reduction of at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker of the pathway being inhibited: epidermal growth factor (EGFR) for Cohort B, sarcoma (Src) for Cohort C, and both EGFR and Src for Cohort D. Blood for these biomarkers will be taken on day of baseline and pre-operatively on day 15. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for pathway in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%).

Recruitment status

TERMINATED

Study phase

EARLY_PHASE1

Target enrollment

9 participants

Primary outcome timeframe

on baseline and preoperatively on day of surgery (day 15)

Results posted on

2014-05-23

Participant Flow

This study was open to accrual from December 2009 to August 2011.

Eleven patients consented, with two ineligible. The study closed prematurely due to slow accrual.

Participant milestones

Participant milestones
Measure	No Treatment Cohort A Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy.	Cetuximab Cohort B Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15	Dasatinib Cohort C Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15	Cetuximab + Dasatiib Cohort D Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15
Overall Study STARTED	9	0	0	0
Overall Study COMPLETED	8	0	0	0
Overall Study NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	No Treatment Cohort A Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy.	Cetuximab Cohort B Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15	Dasatinib Cohort C Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15	Cetuximab + Dasatiib Cohort D Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15
Overall Study Withdrawal by Subject	1	0	0	0

Baseline Characteristics

Cetuximab and/or Dasatinib in Patients With Colorectal Cancer and Liver Metastases That Can Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	No Treatment Cohort A n=9 Participants Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy.	Cetuximab Cohort B Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15	Dasatinib Cohort C Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15	Cetuximab + Dasatiib Cohort D Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 participants n=5 Participants	—	—	—	0 participants n=21 Participants
Age, Categorical Between 18 and 65 years	7 participants n=5 Participants	—	—	—	7 participants n=21 Participants
Age, Categorical >=65 years	2 participants n=5 Participants	—	—	—	2 participants n=21 Participants
Age, Continuous	58 years STANDARD_DEVIATION 1 • n=5 Participants	—	—	—	58 years STANDARD_DEVIATION 1 • n=21 Participants
Gender Female	5 participants n=5 Participants	—	—	—	5 participants n=21 Participants
Gender Male	4 participants n=5 Participants	—	—	—	4 participants n=21 Participants
Region of Enrollment United States	9 participants n=5 Participants	—	—	—	9 participants n=21 Participants

PRIMARY outcome

Timeframe: on baseline and preoperatively on day of surgery (day 15)

Population: No patients accrued to Cohorts B, C, and D, who were to receive the study drugs. Nine patients were accrued in Cohort A; these patients received no study drugs and were to determine normal levels of selected biomarkers. No biomarkers were determined; no data available. This study was closed prematurely due to slow accrual.

Patients who experienced a pre-to-post treatment reduction of at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker of the pathway being inhibited: epidermal growth factor (EGFR) for Cohort B, sarcoma (Src) for Cohort C, and both EGFR and Src for Cohort D. Blood for these biomarkers will be taken on day of baseline and pre-operatively on day 15. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for pathway in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: study entry to day 15

Population: No patients accrued to Cohorts B, C, and D, who were to receive the study drugs. Nine patients were accrued in Cohort A; these patients received no study drugs and were to determine normal levels of selected biomarkers. No biomarkers were determined; no data available. This study was closed prematurely due to slow accrual.

Patients with pre-to-post treatment reduction at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker: total \& phi-EGFR, phi-MAPK, phi-Akt, Ki67, phi-FAK, phi-paxillin, phi-Src, capase 3. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for biomarker in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: weekly to day 15, and at followup on day 30

Population: No patients accrued to Cohorts B, C, and D, which were to receive the study drugs. Nine patients were accrued in Cohort A; these patients received no study drugs and were to determine normal levels of selected biomarkers. No patients were accrued to Cohorts B, C, D. This study was closed prematurely due to slow accrual.

Number of patients with each grade of adverse event (AE) during the specified timeframe using the Common Terminology Criteria for AEs guide, grades 1-5 with one being mild, five is death.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From day 15 (day of surgery) to 30 days after surgery

Population: No patients accrued to Cohorts B, C, and D, which were to receive the study drugs. Nine patients were accrued in Cohort A; these patients received no study drugs and were to determine normal levels of selected biomarkers.No patients received any study drugs. This study was closed prematurely due to slow accrual.

Outcome measures

Outcome data not reported

Adverse Events

No Treatment Cohort A

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cetuximab Cohort B

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dasatinib Cohort C

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cetuximab + Dasatiib Cohort D

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Emily Chan, MD

Vanderbilt-Ingram Cancer Center

Phone: 615-343-4677

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60