- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00730158
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University Comprehensive Cancer Center
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- Hillman CancerCenters
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- Serum potassium within institutional limits of normal (may be corrected with potassium repletion).
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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Arm A
irinotecan+ KD018
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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.
Other Names:
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EXPERIMENTAL: Arm B
irinotecan + placebo
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Irinotecan will be administered intravenously once every 2 weeks from the first cycle, at a dose of 215 mg/m².
Other Names:
Placebo capsules will be administered orally twice a day for 4 days on days 1-4 every 2 weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Participants With Grade 2-4 Toxicities
Time Frame: Up to 3 months after start of study treatment
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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.
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Up to 3 months after start of study treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response (OR)
Time Frame: Up to 36 months
|
Number of participants who experienced a best response of Partial Response (PR) or Stable Disease (SD) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1), PR is >=30% decrease in the sum of the longest diameter of target lesions.
SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameter.
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Up to 36 months
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Progression-free Survival (PFS)
Time Frame: Up to 450 days
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Median number of days and after the treatment participants remained alive without worsening disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
Up to 450 days
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Overall Survival (OS)
Time Frame: Up to 900 days
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Median number of days from the start of treatment that study participants remained alive.
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Up to 900 days
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Clinical Response (CR)
Time Frame: Up to 36 months
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Number of patients that experienced Progressed Disease, Stable Disease or Partial Response per RECIST 1.1.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
(Note: the appearance of one or more new lesions is also considered progression).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters, and Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Up to 36 months
|
The Functional Assessment of Chronic Illness Therapy (Diarrhea) FACIT-D Total Score
Time Frame: Up to 36 months
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The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System is a collection of health-related quality of life (HRQOL) questionnaires targeted to the management of chronic illness.
The Functional Assessment of Chronic Illness Therapy (Diarrhea), the FACIT-D, contains 11 items which address concerns related to treatment-related diarrhea.
Responses are on a Likert scale and range from 0 = "Not at all" to 4 = "Very Much".
Thus, total scores can range from 0 to 44.
Higher scores relate to better functioning.
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Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D - PWB: Physical Well-Being
Time Frame: Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D - PWB: Physical Well-Being is a 7-item subscale score of the total FACIT-D self-assessment that measures a patient's physical well-being.
Individual responses are scale and range from 0 = "Not at all" to 4 = "Very Much".
The total score ranges from 0-28.
Higher scores related to better physical well-being.
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Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D EWB: Emotional Well-Being
Time Frame: Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D Emotional Well-Being (EWB) is a 6-item subscale score of the total FACIT-D self-assessment that measures a patient's emotional well-being.
Individual responses are scale and range from 0 = "Not at all" to 4 = "Very Much".
The total score ranges from 0-24.
Higher scores related to better emotional well-being.
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Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D SWB: Social Well-Being
Time Frame: Up to 36 months
|
The Functional Assessment of Chronic Illness Therapy FACIT-D Social Well-Being (SWB) is a 7-item subset score of the total FACIT-D self-assessment that measures a patient's social well-being.
Individual responses are scale and range from 0 = "Not at all" to 4 = "Very Much".
The total score ranges from 0-28.
Higher scores related to better social well-being.
|
Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D FWB: Functional Well-Being
Time Frame: Up to 36 months
|
The Functional Assessment of Chronic Illness Therapy FACIT-D Functional Well-Being (FWB) is a 7-item subscale of the FACIT-D that measures a patient's functional well-being.
Individual responses are scale and range from 0 = "Not at all" to 4 = "Very Much".
The total score ranges from 0-28.
Higher scores related to better family well-being.
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Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D FACTG: FACT-G Total Score (PWB+SWB+EWB+FWB)
Time Frame: Up to 36 months
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The FACIT-D FACTG: FACT-G Total Score is a total of PWB (Physical Well-Being)+SWB (Social Well-Being)+EWB (Emotional Well-Being)+FWB (Functional Well-Being) subset scores.
Individual responses are scale and range from 0 = "Not at all" to 4 = "Very Much".
The total score ranges from 0-108.
Higher scores indicate greater well-being.
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Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-Fatigue FS: Fatigue Score
Time Frame: Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-Fatigue FS: Fatigue Score is a 13 -item self-reporting assessment that measures fatigue related to their illness.
Individual responses are scale and range from 0 = "Not at all" to 4 = "Very Much".
The total score ranges from 0-52.
Higher scores indicate better functioning.
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Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D TOI: Trial Outcome Index
Time Frame: Up to 36 months
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The Functional Assessment of Chronic Illness Therapy FACIT-D TOI: Trial Outcome Index. is the sum of the Physical Well-Being (PWB), Functional Well-Being (FWB), and "additional concerns" subscales of the FACIT-D.
The TOI is an efficient summary index of physical/functional outcomes.
The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System is a collection of health-related quality of life (HRQOL) questionnaires targeted to the management of chronic illness.
Individual responses are scale and range from 0 = "Not at all" to 4 = "Very Much".
The total score can range from 0-100.
Higher scores relate to better functioning.
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Up to 36 months
|
Metabolites and Cytokine Scoring for Prediction of Time to Disease Progression
Time Frame: Up to 36 months
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Number of patients with metabolites in their blood samples with a score less than 4.8 and greater than 4.8.
A Cox Proportional Hazard Regression Analysis was fitted using survival time, status to the cytokines and metabolites as covariates.
The analysis computes beta coefficients (hazard ratios) for each cytokine/metabolite.
Scores higher than a threshold value of 4.8 were associated with higher overall survival than patients who scored less than 4.8.
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Up to 36 months
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Uridine Diphosphate Glucuronosyltransferase (UGT) 1A1 Alleles
Time Frame: From 30 minutes prior to irinotecan infusion through to Immediately after irinotecan infusion, up to 8 weeks
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The number of patients with specific polymorphisms of UGT1A1 using genotype analysis of peripheral blood sample.
UGT1A1*1 is the wild-type allele associated with normal enzyme activity.
Patients with genotypic status of 7/7 are at an increased risk of neutropenia following intravenous irinotecan therapy.
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From 30 minutes prior to irinotecan infusion through to Immediately after irinotecan infusion, up to 8 weeks
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Circulating Tumor DNA - Percentage of Patients With DNA Mutations
Time Frame: Baseline - prior to treatment
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Percentage of patients with Braf, Kras, Nras, PIK3CA and PTEN mutations associated with tumor detected in the circulating DNA of plasma, before treatment.
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Baseline - prior to treatment
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Circulating Tumor DNA - Percentage of Patients With DNA Mutations
Time Frame: End of treatment - up to 8 weeks
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Percentage of patients with Braf, Kras, Nras, PIK3CA and PTEN mutations associated with tumor detected in the circulating DNA of plasma, before treatment.
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End of treatment - up to 8 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Edward Chu, MD, Hillman Cancer Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Irinotecan
Other Study ID Numbers
- 12-005
- ACS IRG 58-012-49
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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