A Clinical Study of PHY906 as a Modulator of CPT-11 in Patients With Metastatic Colorectal Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Yale University.
Recruitment status was  Recruiting
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
First received: August 4, 2008
Last updated: June 5, 2009
Last verified: June 2009

PHY906 is an oral form of a spray dried aqueous extract composed of four main herbs, which have been used in the Orient for nearly 2000 years for a variety of GI symptoms including diarrhea and nausea/vomiting. Extensive pre-clinical research has been done with Chinese herbal medicine, and studies have documented significant anticancer activity in combination with various cytotoxic agents including CPT-11, which is a semi-synthetic derivative of the natural alkaloid camptothecin and belongs to the class of topoisomerase I inhibitors. 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 PHY906 is its potential activity in reducing chemotherapy-induced toxicity, especially diarrhea.

Condition Intervention Phase
Colorectal Neoplasms
Drug: PHY906
Drug: CPT-11
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IB/II Multi-Center Clinical Study of PHY906 as a Modulator of CPT-11 Chemotherapy in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:

Further study details as provided by Yale University:

Primary Outcome Measures:
  • To determine maximum tolerated dose of PHY906 when combined with a standard dose of CPT-11 and to determine response rate in patients with metastatic colorectal cancer [ Time Frame: Maximum tolerated dose will be available at end of Phase I while response rate will be available upon completion of study. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine progression-free survival and overall survival [ Time Frame: upon completion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: December 2008
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: PHY906
    Traditional Chinese Medicine formulation administered orally twice a day for 4 days on days 1-4 every 2 weeks from the second cycle, beginning at a dose of 1,800 mg twice a day, and escalating to 2,400 mg twice a day in dose level 2-4.
    Drug: CPT-11
    CPT-11 will be administered intravenously once every 2 weeks from the first cycle, beginning at a dose of 180 mg/m², and escalating to 215 mg/m²in dose level 3 and 250 mg/m² in dose level 4.
    Other Names:
    • Irinotecan
    • Camptosar

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective (Phase I Part).
  • Patients with histologically confirmed metastatic colorectal cancer, who failed with prior two different chemotherapy regimens (Phase II Part).
  • At least one evaluable lesion. Lesions must be evaluated by computerized tomography (CT), magnetic resonance imaging (MRI), or PET scan (Phase I Part).
  • At least one measurable lesion by CT or MRI of ≥ 20 mm (if conventional CT scan) or ≥ 10 mm (if spiral CT scan) (Phase II part)
  • Karnofsky Performance Status ≥ 60%
  • Must be ≥18 years of age.
  • Expected survival of at least 3 months for phase I part, and at least 6 months for phase II part.
  • 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 PHY906 and CPT-11 on a fetus or nursing child are unknown.
  • Must be able and willing to give written informed consent.
  • Patients must have the following clinical laboratory values:

ANC count ≥ 1,500/ mm3. Platelets ≥ 100,000/ mm3. Serum creatinine ≤ 2x upper limit of normal. Total bilirubin < 1.5x upper limit of normal. Serum calcium < 12.0 mg/dl. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x the upper limit of normal (≤ 5.0 x ULN is acceptable if liver has tumor involvement) Prothrombin Time (PT), activated partial thromboplastin time (aPTT) and INR ≤ 1.5 x ULN or in the therapeutic range if on anticoagulation Hemoglobin ≥ 9 gm/dl (may be corrected by transfusion).

Exclusion Criteria:

  • 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.
  • 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.
  • Known HIV positivity, as safety in this patient population has not been assessed.
  • 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 last 4 weeks.
  • Patients taking concurrent medications of any kind which are strong inducers or inhibitors of 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00730158

Contact: Lois Ravage-Mass, RN 203-785-4991 lois.ravage-mass@yale.edu
Contact: Lynne Lamb, RN 203-737-2562 lynne.lamb@yale.edu

United States, Connecticut
Yale University Comprehensive Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Contact: Lois Ravage-Mass, RN    203-785-4991    lois.ravage-mass@yale.edu   
Contact: Lynne Lamb, R.N.    203-737-2562    lynne.lamb@yale.edu   
Principal Investigator: Wasif Saif, MD         
VACT Cancer Center Not yet recruiting
West Haven, Connecticut, United States, 06516
Contact: Michal Rose, M.D.    203-937-3421      
Sponsors and Collaborators
Yale University
Principal Investigator: Wasif Saif, MD Yale University Comprehensive Cancer Center
  More Information

No publications provided by Yale University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Wasif Saif, M.D., Principal Investigator, Yale University School of Medicine
ClinicalTrials.gov Identifier: NCT00730158     History of Changes
Other Study ID Numbers: 0706002781, ACS IRG 58-012-49
Study First Received: August 4, 2008
Last Updated: June 5, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014