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Colorectal NeoplasmsPhase 2NCT00730158

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

A Phase 2 study testing KD018 and Irinotecan in people with Colorectal Neoplasms, run by Edward Chu, MD at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Neoplasms
What is being tested?
KD018 and Irinotecan
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
33 participants
Where
2 sitesUnited States
Study dates
Dec 2008to Jun 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Yale University Comprehensive Cancer Center

    New Haven, Connecticut, 06520

  • Hillman CancerCenters

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

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.

Read the detailed description

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. Irinotecan has been evaluated extensively as a single agent as well as in combination with other cytotoxic agents in several schedules. We recently completed a phase I study of irinotecan using the every-2-week schedule in combination with varying doses of KD018. Based on this phase I study, the dose of irinotecan that will be used in this study is 215 mg/m2.

Being tested
KD018, Irinotecan, Placebo
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KD018Drug

    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.

  • IrinotecanDrug

    Also called Camptosar, CPT-11

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

  • PlaceboDrug

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

Study groups in NCT00730158
Study groupRoleWhat they receive
Arm AExperimentalirinotecan+ KD018
Receives: Drug: KD018; Drug: Irinotecan
Arm BExperimentalirinotecan + placebo
Receives: Drug: Irinotecan; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 3 months after start of study treatment

Secondary outcomes (16)

  1. Overall Response (OR)

    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.

    Measured: Up to 36 months

  2. Progression-free Survival (PFS)

    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).

    Measured: Up to 450 days

  3. Overall Survival (OS)

    Median number of days from the start of treatment that study participants remained alive.

    Measured: Up to 900 days

  4. Clinical Response (CR)

    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.

    Measured: Up to 36 months

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

    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.

    Measured: Up to 36 months

  6. The Functional Assessment of Chronic Illness Therapy FACIT-D - PWB: Physical Well-Being

    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.

    Measured: Up to 36 months

  7. The Functional Assessment of Chronic Illness Therapy FACIT-D EWB: Emotional Well-Being

    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.

    Measured: Up to 36 months

  8. The Functional Assessment of Chronic Illness Therapy FACIT-D SWB: Social Well-Being

    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.

    Measured: Up to 36 months

  9. The Functional Assessment of Chronic Illness Therapy FACIT-D FWB: Functional Well-Being

    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.

    Measured: Up to 36 months

  10. The Functional Assessment of Chronic Illness Therapy FACIT-D FACTG: FACT-G Total Score (PWB+SWB+EWB+FWB)

    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.

    Measured: Up to 36 months

  11. The Functional Assessment of Chronic Illness Therapy FACIT-Fatigue FS: Fatigue Score

    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.

    Measured: Up to 36 months

  12. The Functional Assessment of Chronic Illness Therapy FACIT-D TOI: Trial Outcome Index

    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.

    Measured: Up to 36 months

  13. Metabolites and Cytokine Scoring for Prediction of Time to Disease Progression

    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.

    Measured: Up to 36 months

  14. Uridine Diphosphate Glucuronosyltransferase (UGT) 1A1 Alleles

    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.

    Measured: From 30 minutes prior to irinotecan infusion through to Immediately after irinotecan infusion, up to 8 weeks

  15. Circulating Tumor DNA - Percentage of Patients With DNA Mutations

    Percentage of patients with Braf, Kras, Nras, PIK3CA and PTEN mutations associated with tumor detected in the circulating DNA of plasma, before treatment.

    Measured: Baseline - prior to treatment

  16. Circulating Tumor DNA - Percentage of Patients With DNA Mutations

    Percentage of patients with Braf, Kras, Nras, PIK3CA and PTEN mutations associated with tumor detected in the circulating DNA of plasma, before treatment.

    Measured: End of treatment - up to 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2008 (estimated)
  2. Study startDec 2008
  3. Primary completionJun 2016
  4. Study completionJun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00730158
Sponsor's protocol ID
12-005
Other IDs
ACS IRG 58-012-49
Status last verified
Apr 2019
First submitted
4 Aug 2008
Last updated
22 May 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20720216

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing KD018 and Irinotecan in people with Colorectal Neoplasms, run by Edward Chu, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants With Grade 2-4 Toxicities (time frame: Up to 3 months after start of study treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00730158, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2019.

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