Clinical trial NCT02723578: Pemetrexed and Erlotinib for Metastatic Colorectal Cancer
Official title: A Phase 2 Study of Pemetrexed and Erlotinib for Metastatic Colorectal Cancer Refractory to Standard Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2016-03-30
Enrollment: 50
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Overall response rate
timeFrame: up to 2 years
measure: Progression-free survival
timeFrame: up to 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: up to 2 years
measure: Disease control rate
timeFrame: up to 2 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 2 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
Study officials:
affiliation: Yonsei Cancer Center, Yonsei University Health System
name: Joong Bae Ahn
role: PRINCIPAL_INVESTIGATOR
References: