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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Pittsburgh
Sponsor:
Collaborator:
Kadmon Pharmaceuticals
Information provided by (Responsible Party):
Edward Chu, MD, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00730158
First received: August 4, 2008
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

KD018 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 Irinotecan, 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 KD018 is its potential activity in reducing chemotherapy-induced toxicity, especially diarrhea.


Condition Intervention Phase
Colorectal Neoplasms
Drug: KD018
Drug: Irinotecan
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • The effect of KD018 on 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 [ 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:
  • The effect of KD018 on irinotecan overall response rate (RR). [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]
  • The effect of KD018 on irinotecan progression-free survival (PFS). [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]
  • The effect of KD018 on irinotecan overall survival (OS) [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 165
Study Start Date: December 2008
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
irinotecan+ KD018
Drug: KD018
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: Irinotecan
Irinotecan 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
  • CPT-11
Experimental: Arm B
irinotecan + placebo
Drug: Irinotecan
Irinotecan 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
  • CPT-11
Drug: Placebo
Placebo capsules will be administered orally twice a day for 4 days on days 1-4 every 2 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00730158

Contacts
Contact: Rita Johnson (412) 647-8571 johnsonr1@upmc.edu

Locations
United States, Connecticut
Yale University Comprehensive Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Contact: Howard Hochster, MD    203-785-5756    howard.hochster@yale.edu   
Principal Investigator: Howard Hochester, MD         
United States, Pennsylvania
Hillman CancerCenters Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Edward Chu, MD    412-648-6589    chue2@upmc.edu   
Principal Investigator: Edward Chu, MD         
Sponsors and Collaborators
University of Pittsburgh
Kadmon Pharmaceuticals
Investigators
Principal Investigator: Edward Chu, MD Hillman Cancer Center
  More Information

No publications provided by University of Pittsburgh

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Edward Chu, MD, Principal Investigator, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00730158     History of Changes
Other Study ID Numbers: 12-005, ACS IRG 58-012-49
Study First Received: August 4, 2008
Last Updated: June 13, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 21, 2014