Pemetrexed and Erlotinib for Metastatic Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT02723578
• Recruitment Status: Completed
• First Posted: March 30, 2016
• Last Update Posted: January 13, 2020
• Sponsor: Yonsei University
• Information provided by (Responsible Party): Joong Bae Ahn, Yonsei University

Study Description

Brief Summary:

Pemetrexed is a multitargeted antifolate, which primarily inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase in the folate-dependent metabolic process. Nowadays, pemetrexed is used to treat malignant pleural mesothelioma and non-squamous non-small cell lung cancer. Preclinical and clinical studies showed that pemetrexed had cytotoxic activity in many kinds of cancers including colorectal cancer. Erlotinib is a tyrosine-kinase inhibitor of EGFR, which was approved for the treatment of non-small cell lung cancer. Erlotinib also showed activity to colorectal cancer cells. Recently, Zhang et al. demonstrated synergistic cytotoxicity of pemetrexed and gefitinib in preclinical study.

In this multicenter, non randomized, open label phase II study, investigators aimed to evaluate the efficacy and safety of Pemetrexed and Erlotinib combination.

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer	Drug: Pemetrexed; Drug: Erlotinib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Pemetrexed and Erlotinib for Metastatic Colorectal Cancer Refractory to Standard Chemotherapy
• Actual Study Start Date: December 1, 2015
• Actual Primary Completion Date: August 2018
• Actual Study Completion Date: December 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pemetrexed and Erlotinib; Pemetrexed 500 mg/m2 IV over 10 minutes on day 1 every 21 days and Erlotinib 150 mg PO once daily on days 1-21 every 21 days	Drug: Pemetrexed; Pemetrexed 500 mg/m2 IV over 10 minutes on day 1 every 21 days; Drug: Erlotinib; Erlotinib 150 mg PO once daily on days 1-21 every 21 days

Outcome Measures

Primary Outcome Measures :

1. Overall response rate [ Time Frame: up to 2 years ]
2. Progression-free survival [ Time Frame: up to 2 years ]

Secondary Outcome Measures :

1. Overall survival [ Time Frame: up to 2 years ]
2. Disease control rate [ Time Frame: up to 2 years ]
3. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female, aged ≥ 19 years
2. Histologic or cytologic confirmed diagnosis of colorectal carcinoma with metastatic (STAGE IV) disease.
3. Confirmed KRAS(codon 12 or 13) status
4. Prior chemotherapy for metastatic disease is required; prior regimens must include fluoropyrimidine, oxaliplatin and irinotecan
5. Eastern Cooperative Oncology Group performance status ≤ 2
6. Patients who can swallow oral medication.
7. Life expectancy of greater than 3 months

8. Patients must have normal organ and marrow function as defined below:

   • absolute neutrophil count ≥ 1,500/mm3
   • hemoglobin ≥ 9 g/dl
   • platelets ≥ 100,000/mm3
   • serum total bilirubin ≤ 1.5 X institutional upper limit of normal
   • aspartate aminotransferase(SGOT)/alanine aminotransferase(SGPT) ≤ 3.0 X institutional upper limit of normal (≤ 5 times the upper institutional limits of normal if hepatic metastases are present)
   • serum creatinine ≤ 1.5 times the institutional upper limits of normal or Creatinine Clearance ≥ 50ml/min
9. The effects of Pemetrexed and Erlotinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception (hormonal or barrier method of birth control; abstinence) during the study and for 6 months thereafter. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
10. Participant is willing and able to give informed consent for participation in the study. Voluntary signed and dated written informed consent form in accordance with regulatory and institutional guidelines obtained before the performance of any protocol-related procedures not part of normal patient care.

Exclusion Criteria:

1. Previous treatment with Pemetrexed and Erlotinib
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pemetrexed or Erlotinib or other agents used in the study
3. Patients who can not allow the administration of Folic acid or Vitamin B12.
4. Past or current history of neoplasm other than colorectal carcinoma with a disease-free interval of less than 5 years, except for non-melanoma skin cancer or curatively treated carcinoma in situ of the cervix.
5. Systemic chemotherapy within three weeks after the administration of the last before the test treatment
6. Major surgical operation or major trauma within 4 weeks.
7. Patients who have had wide-ranged radiotherapy within 4 weeks or limited radiotherapy within 2 2 weeks.
8. Persistent toxicity (> CTCAE grade 1) related to previous treatment except for the hair loss.
9. Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
11. Breast-feeding or pregnant female

Contacts and Locations

Locations

Korea, Republic of

Yonsei University Health System, Severance Hospital

Seoul, Korea, Republic of, 03722

Sponsors and Collaborators

Yonsei University

Investigators

• Principal Investigator: Joong Bae Ahn; Yonsei Cancer Center, Yonsei University Health System

More Information

• Responsible Party: Joong Bae Ahn, Professor, Yonsei University
• ClinicalTrials.gov Identifier: NCT02723578
• Other Study ID Numbers: 4-2015-0617
• First Posted: March 30, 2016
• Last Update Posted: January 13, 2020
• Last Verified: January 2020

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Erlotinib Hydrochloride; Pemetrexed; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors