Pemetrexed Plus Tarceva as Salvage Treatment in EGFR Overexpressed Metastatic Colorectal Cancer Patients Who Were Failed After Standard Chemotherapy
Primary Purpose
Colo-rectal Cancer
Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Pemetrexed
Tarceva 100Mg Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Colo-rectal Cancer
Eligibility Criteria
Inclusion Criteria:
Advanced colorectal cancer failed from all standard chemotherapy
- History of refractoriness from chemotherapy including 5-FU, Oxaliplatin, Irinotecan
- Oral 5-FU agents are included standard chemotherapy
- Targeted agents such as cetuximab or bevacizumab are not included in inclusion criteria
- Patient must have willingness and ability to comply with the study protocol including visiting hospital for test and treatment during trial
- ECOG performance status 0~2
- Measurable lesion (RECIST 1.1) must exist
- Expected survival should be more than 3 months from first dose of pemetrexed
- Adequate organ function as defined as below estimated 28 days before first doe of pemetrexed:
Exclusion Criteria:
- Poor performance status (ECOG PS ≥ 3)
- Patient can not take folic acid or Vitamin B12.
- History of previous treatment with pemetrexed
- History of malignant disease, except: non-melanoma skin cancer that properly treated, cured uterine cervical cancer or other solid tumor without evidence of recurrence within 5 years
- Patient can not swallow oral pills.
- Treatment with medication of clinical trial within 14 days (or longer duration according to specific agents)
- Systemic chemotherapy or radiation (except palliative purpose) within 3 weeks (or longer duration according to specific agents)
- Toxicity from previous treatment as CTCAE grade > 1, except alopecia
- bowel obstruction or CTCAE grade 3/4 upper GI bleeding before 4 weeks
- QTc prolongation (QTc > 480msec) at resting is documented more than twice within 24 hours or family history of QT prolongation syndrome
Sites / Locations
- Samsung Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pemetrexed+Tarceva
Arm Description
Pemetrexed 500 mg/m2 IV Q 3 weeks Tarceva 100mg once daily, continous
Outcomes
Primary Outcome Measures
Overall Response Rate
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03086538
Brief Title
Pemetrexed Plus Tarceva as Salvage Treatment in EGFR Overexpressed Metastatic Colorectal Cancer Patients Who Were Failed After Standard Chemotherapy
Official Title
Pemetrexed Plus Tarceva as Salvage Treatment in EGFR Overexpressed Metastatic Colorectal Cancer Patients Who Were Failed After Standard Chemotherapy: A Phase II Single Arm Prospective Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
May 30, 2017 (Actual)
Primary Completion Date
January 30, 2020 (Actual)
Study Completion Date
May 25, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
This study is single center single arm prospective phase II study. In this study, efficacy and side effects of pemetrexed as salvage regimen on patients who failed all standard chemotherapy and total of 29 patients will be enrolled. Pemetrexed will be continued until disease progression is happened.
Detailed Description
Antitumor effect of pemetrexed is already proven lung cancer, pleural mesothelioma, peritoneal mesothelioma and has been used as a standard therapeutic agent. In addition, this drug does not have severe side effects, pemetrexed is thought to be an important option for patients with poor performance status or elderly patients. Pemetrexed has been studied in colorectal cancer, Zhang et al have demonstrated that pemetrexed combined with gefitinib has a significantly synergistic effect on colorectal cancer cells (17). In two phase II studies in which patients received pemetrexed as first-line treatment for metastatic disease, objective response rates were 15 - 17 %. These trials were conducted prior to supplementation with folic acid and vitamin B12, which markedly decreased the frequency of hematologic toxicities of pemetrexed; routine supplementation is now included in all clinical trials of the agent (18).
Erlotinib (tarceva) is oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Erlotinib showed the effect in the maintanence therapy (combined with bevacizumab) in colorector cancer. Also, erolitinib had the effect in biliary tract cancer and pancreatic cancer. Our previous phase III trial for tarceva puls GEMOX (gemcitabine plus oxaliplatin) reported that adding to tarceva to GEMOX had more useful in the specific subgroup with EFGR overexpressed patients.
The aim of present study is to assess treatment efficacy and side effects of pemetrexed plus tarceva on EGFR overexpressed patients with refractory colorectal cancer and no treatment option whose performance status is relatively preserved.
<Pre-medication for Alimta> D-7 ~ Folic acid 1mg QD PO D-7 ~ Vitamin B12 1mg/9weeks IM D-1, D1, D2 Dexamethasone 4mg BID PO
<Treatment> D1 Alimta 500mg/m2 + NS 100ml IV infusion for 10mins Every 3weeks
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colo-rectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Pemetrexed 500 mg/m2 IV Q 3 weeks Tarceva 100mg once daily, continous
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pemetrexed+Tarceva
Arm Type
Experimental
Arm Description
Pemetrexed 500 mg/m2 IV Q 3 weeks Tarceva 100mg once daily, continous
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
Pemetrexed is a multitarget antifolate (MTA) whose mechanism of action relies mainly on the inhibition of TS, with weaker secondary effects on glycinamide ribonucleotide formyltransferase (GARFT) and dihydrofolate reductase (DHFR), leading to impairment of DNA synthesis and repair.
Intervention Type
Drug
Intervention Name(s)
Tarceva 100Mg Tablet
Intervention Description
Erlotinib (tarceva) is oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).
Primary Outcome Measure Information:
Title
Overall Response Rate
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Advanced colorectal cancer failed from all standard chemotherapy
History of refractoriness from chemotherapy including 5-FU, Oxaliplatin, Irinotecan
Oral 5-FU agents are included standard chemotherapy
Targeted agents such as cetuximab or bevacizumab are not included in inclusion criteria
Patient must have willingness and ability to comply with the study protocol including visiting hospital for test and treatment during trial
ECOG performance status 0~2
Measurable lesion (RECIST 1.1) must exist
Expected survival should be more than 3 months from first dose of pemetrexed
Adequate organ function as defined as below estimated 28 days before first doe of pemetrexed:
Exclusion Criteria:
Poor performance status (ECOG PS ≥ 3)
Patient can not take folic acid or Vitamin B12.
History of previous treatment with pemetrexed
History of malignant disease, except: non-melanoma skin cancer that properly treated, cured uterine cervical cancer or other solid tumor without evidence of recurrence within 5 years
Patient can not swallow oral pills.
Treatment with medication of clinical trial within 14 days (or longer duration according to specific agents)
Systemic chemotherapy or radiation (except palliative purpose) within 3 weeks (or longer duration according to specific agents)
Toxicity from previous treatment as CTCAE grade > 1, except alopecia
bowel obstruction or CTCAE grade 3/4 upper GI bleeding before 4 weeks
QTc prolongation (QTc > 480msec) at resting is documented more than twice within 24 hours or family history of QT prolongation syndrome
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
31820199
Citation
Kim ST, Hong JY, Lee J, Park JO, Lim HY, Kang WK, Park YS. Pemetrexed/Erlotinib as a Salvage Treatment in Patients with High EGFR-Expressing Metastatic Colorectal Cancer Following Failure of Standard Chemotherapy: A Phase II Single-Arm Prospective Study. Target Oncol. 2020 Feb;15(1):67-73. doi: 10.1007/s11523-019-00691-z.
Results Reference
derived
Learn more about this trial
Pemetrexed Plus Tarceva as Salvage Treatment in EGFR Overexpressed Metastatic Colorectal Cancer Patients Who Were Failed After Standard Chemotherapy
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