Irinotecan Hydrochloride with or without Chinese Herbal Formulation PHY906 in Treating Patients with Metastatic Colorectal Cancer

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IITreatmentActive18 and overUPCI 12-005
NCI-2016-00749, NCT00730158

Trial Description

Summary

This randomized phase II trial studies the side effects and how well irinotecan hydrochloride with or without Chinese herbal formulation PHY906 works in treating patients with colorectal cancer which has spread to other places in the body. Drugs used in chemotherapy, such as irinotecan hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chinese herbal formulation PHY906 may help decrease gastrointestinal side effects caused by treatment with irinotecan hydrochloride. Giving Chinese herbal formulation PHY906 with chemotherapy may kill more tumor cells.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine the effect of Chinese herbal formulation PHY906 (KD018) on irinotecan hydrochloride (irinotecan) toxicity with the goal of achieving a 30% reduction in the overall incidence of grade 2-4 toxicity during the first 3 months of the study treatment.

SECONDARY OBJECTIVES:

I. To determine the effect of KD018 on irinotecan overall response rate (RR).

II. To determine the effect of KD018 on irinotecan progression-free survival (PFS).

III. To determine the effect of KD018 on irinotecan overall survival (OS).

IV. To evaluate the metabolomic profiles associated with irinotecan and KD018 treatment.

V. To investigate the biological effect of KD018 on irinotecan chemotherapy using a series of biomarker analyses.

VI. To evaluate the effect of KD018 on quality of life associated with irinotecan chemotherapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on day 1 and Chinese herbal formulation PHY906 orally (PO) twice daily (BID) on days 1-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive irinotecan hydrochloride IV over 90 minutes on day 1 and a placebo PO BID on days 1-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 3 months for 3 years.

Eligibility Criteria

Inclusion Criteria:

Patients with histologically confirmed metastatic colorectal cancer, who have received and/or progressed on a prior oxaliplatin-based chemotherapy regimen

Patients must have been off of chemotherapy for at least 4 weeks prior to day 1 of cycle 1; informed consent can be signed at any time prior to the start of therapy

Patients with wild-type or mutant Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) metastatic colorectal cancer (mCRC)

At least one measurable lesion by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Expected survival of at least 6 months

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

Must be able and willing to give written informed consent

Absolute neutrophil count (ANC) >= 1,500/ mm^3

Platelets >= 100,000/ mm^3

Hemoglobin >= 9 gm/dL (may be corrected by transfusion)

Bilirubin < 1.5 x upper limit of normal (ULN)

Aspartate aminotransferase (AST) =< 2.5 x ULN or alanine aminotransferase (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)

Serum creatinine =< 2 x ULN

Serum potassium within institutional limits of normal (may be corrected with potassium repletion)

All subjects must be capable of swallowing multiple capsules

Exclusion Criteria:

Continued treatment with bevacizumab with documented evidence of disease progression on a bevacizumab-containing regimen

Uncontrolled or symptomatic brain metastasis

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

Unwilling or unable to follow protocol requirements or to give informed consent

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

Known human immunodeficiency virus (HIV) positivity

Presence of metastatic disease that, in the opinion of investigators, would require palliative treatment within 4 weeks of enrollment

Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies

Pregnant or breast-feeding women

Men and women of childbearing age and potential, who are not willing to use effective contraception

Major surgery within the previous 4 weeks

Patients taking concurrent medications of any kind which are strong inducers or inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4); patients receiving any of the following will be excluded: ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John’s wort

Patients previously treated with irinotecan-containing regimen

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Yale University

  • National Cancer Institute
Edward Chu, Principal Investigator

Trial Sites

U.S.A.

Connecticut
New Haven

Yale University

Howard S. Hochster
Ph: 203-785-5756
Email: howard.hochster@yale.edu

Howard S. Hochster
Principal Investigator

Pennsylvania
Pittsburgh

University of Pittsburgh Cancer Institute (UPCI)

Edward Chu
Ph: 412-648-6589
Email: chue2@upmc.edu

Edward Chu
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00730158

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.