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

NCT00730158 | Completed Phase 2 Results DMC

• 2 other identifiers: 12-005ACS IRG 58-012-49
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Grade 2-4 Toxicities

  The proportion of participants with a toxicity grade greater than or equal to grade 2, per NCI CTCAE 4.0. Toxicity is defined as any adverse event (AE) at least probably related to treatment occurring with 90 days of the beginning of treatment. The worst grade of AE at least probably related to treatment was determined for each participant.

  Up to 3 months after start of study treatment

Secondary Outcomes (16)

• Overall Response (OR)

  Up to 36 months

• Progression-free Survival (PFS)

  Up to 450 days

• Overall Survival (OS)

  Up to 900 days

• Clinical Response (CR)

  Up to 36 months

• The Functional Assessment of Chronic Illness Therapy (Diarrhea) FACIT-D Total Score

  Up to 36 months

Study Arms (2)

Arm A

EXPERIMENTAL

irinotecan+ KD018

Drug: KD018; Drug: Irinotecan

Arm B

EXPERIMENTAL

irinotecan + placebo

Drug: Irinotecan; Drug: Placebo

Interventions

KD018 DRUG

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.

Arm A

Irinotecan DRUG

Irinotecan will be administered intravenously once every 2 weeks from the first cycle, at a dose of 215 mg/m².

Also known as: Camptosar, CPT-11

Arm A; Arm B

Placebo DRUG

Placebo capsules will be administered orally twice a day for 4 days on days 1-4 every 2 weeks.

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed metastatic colorectal cancer (mCRC), 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 signing the informed consent/start of screening.
• Patients with wild-type or mutant KRAS mCRC.
• At least one measurable lesion by RECIST 1.1.
• ECOG PS Performance Status 0-2.
• Must be \>/=18 years of age.
• 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. Pregnant and nursing patients are excluded because the effects of the combination of KD018 and irinotecan 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.
• Hemoglobin \>/= 9 gm/dL (may be corrected by transfusion).
• 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)
• Serum creatinine \</=2 x ULN

You may not qualify if:

• 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.
• 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 the investigator, 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 CYP3A4.
• Patients previously treated with an irinotecan-containing regimen.

Sponsors & Collaborators

• Edward Chu, MD: lead
• Kadmon Corporation, LLC: collaborator

Study Sites (2)

Yale University Comprehensive Cancer Center

New Haven, Connecticut, 06520, United States

Location

Hillman CancerCenters

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Lam W, Bussom S, Guan F, Jiang Z, Zhang W, Gullen EA, Liu SH, Cheng YC. The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Transl Med. 2010 Aug 18;2(45):45ra59. doi: 10.1126/scitranslmed.3001270.

  PMID: 20720216 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Edward Chu, MD
• Organization: UPMC Hillman Cancer Center

chue2@upmc.edu

(412) 648-6589

Study Officials

• Edward Chu, MD

  Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 4, 2008
• First Posted: August 8, 2008
• Study Start: December 1, 2008
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2018
• Last Updated: May 22, 2019
• Results First Posted: May 22, 2019

Record last verified: 2019-04

Locations

US (2)