A Phase II Multicenter, Randomized, Placebo Controlled, Double Blinded Clinical Study of KD018 as a Modulator of Irinotecan Chemotherapy in Patients With Metastatic Colorectal Cancer
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: KD018; Irinotecan; Placebo
Intervention description: Traditional Chinese Medicine formulation administered orally twice a day for 4 days on days 1-4 every 2 weeks from the second cycle, at a dose of 1,800 mg, twice a day.; Irinotecan will be administered intravenously once every 2 weeks from the first cycle, at a dose of 215 mg/m².; Placebo capsules will be administered orally twice a day for 4 days on days 1-4 every 2 weeks.
Intervention MeSH terms: Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The proposed plan will investigate the mechanism and efficacy of Chinese herbal medicine as
      an adjunct to chemotherapy in treatment of patients with metastatic colorectal cancer. Our
      rationale for the therapeutic use of KD018 is its potential activity in reducing
      chemotherapy-induced toxicity, especially diarrhea.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histologically confirmed metastatic colorectal cancer (mCRC), who have
             received and/or progressed on a prior oxaliplatin-based chemotherapy regimen.

          2. Patients must have been off of chemotherapy for at least 4 weeks prior to signing the
             informed consent/start of screening.

          3. Patients with wild-type or mutant KRAS mCRC.

          4. At least one measurable lesion by RECIST 1.1.

          5. ECOG PS Performance Status 0-2.

          6. Must be >/=18 years of age.

          7. Expected survival of at least 6 months.

          8. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically
             sterile) must use acceptable contraceptive methods (abstinence, intrauterine device
             [IUD], oral contraceptive or double barrier device), and must have a negative serum or
             urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing
             patients are excluded. Sexually active men must also use acceptable contraceptive
             methods. Pregnant and nursing patients are excluded because the effects of the
             combination of KD018 and irinotecan on a fetus or nursing child are unknown.

          9. Must be able and willing to give written informed consent.

         10. Patients must have the following clinical laboratory values:

               1. ANC count >/= 1,500/ mm3.

               2. Platelets >/= 100,000/ mm3.

               3. Hemoglobin >/= 9 gm/dL (may be corrected by transfusion).

         11. Evidence of adequate hepatic function, Bilirubin < 1.5 x upper limit of normal (ULN)
             AST </= 2.5 x ULN or ALT </= 2.5 x ULN (Note, if both AST and ALT are done, both must
             be </= 2.5 x ULN) OR AST </= 5.0 x ULN or ALT </= 5.0 x ULN is acceptable if liver has
             tumor involvement. (Note, if both AST and ALT are done, both must be </= 5.0 x ULN)

         12. Serum creatinine </=2 x ULN

         13. Serum potassium within institutional limits of normal (may be corrected with potassium
             repletion).

        Exclusion Criteria:

          1. Continued treatment with bevacizumab with documented evidence of disease progression
             on a bevacizumab-containing regimen.

          2. Uncontrolled or symptomatic brain metastasis.

          3. Serious concomitant systemic disorders (e.g., active infection) that, in the opinion
             of the investigator, would compromise the safety of the patient or compromise the
             patient's ability to complete the study.

          4. Unwilling or unable to follow protocol requirements or to give informed consent.

          5. No treatment with cytotoxic or biologic agents within the 4 weeks prior to beginning
             treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 4 weeks must
             have elapsed from any prior surgery, radiation, hormonal or other drug therapy for
             their cancer.

          6. Known HIV positivity, as safety in this patient population has not been assessed.

          7. Presence of metastatic disease that, in the opinion of the investigator, would require
             palliative treatment within 4 weeks of enrollment.

          8. Altered mental status precluding understanding of the informed consent process and/or
             completion of the necessary studies.

          9. Pregnant or breast-feeding women.

         10. Men and women of childbearing age and potential, who are not willing to use effective
             contraception.

         11. Major surgery within the previous 4 weeks.

         12. Patients taking concurrent medications of any kind which are strong inducers or
             inhibitors of CYP3A4.

         13. Patients previously treated with an irinotecan-containing regimen.