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Pilot Trial of KD018 With Neo-Adjuvant Concurrent Chemo-Radiation Therapy in Patients With Locally Advanced Rectal Cancer

Primary Purpose

Rectal Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Chemo with concomitant Capecitabine and KD018

About this trial

This is an interventional treatment trial for Rectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have histologically confirmed T3-T4 and N0-N2, M0 adenocarcinoma of the rectum with the inferior margin within 16 cm from the anal verge.
Patients must have had a Transrectal ultrasound (TRUS)/endoscopic ultrasound (TEUS) staging within two months prior to treatment start.
Patients must have had a pelvic MRI within 28 days prior to the initiation of treatment.
Patient must have the ability to swallow multiple capsules.
Women of child bearing potential between the ages of 18 and 60 years of age must have a negative urine pregnancy test prior to undergoing simulation in preparation for radiation therapy to the pelvis.
ECOG performance status of 0 to 1 within 28 days prior to initiation of treatment.
Patients must have normal organ and marrow function as defined below. All laboratory values must be obtained within 14 days prior to initiation of treatment:
absolute neutrophil count >= 1,500/mcL
platelets >= 100,000/mcL
hemoglobin >= 8.0 g/ dL
serum bilirubin < 1.5 times the upper limit of of normal (ULN)
serum AST, ALT < 2.5 times ULN
serum Creatinine ≤ 1.5 times ULN
The effects of radiation on the developing human fetus are known to be teratogenic. For this reason, all women and sexually active men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

History of clinically significant Crohn's disease or inflammatory bowel disease (IBD).
Active collagen vascular disease.
History of previous abdominal or pelvic radiation therapy.
History of previous systemic chemotherapy unless given curatively for other malignancy now > 5 years without evidence of recurrence.
Patients with suspected or confirmed poor compliance, mental instability, or prior or current alcohol or drug abuse deemed by the investigator to be likely to affect their ability to sign the informed consent, or undergo study procedures will be excluded.
Pregnant women are excluded from this study because radiation has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with either KD018 or Capecitabine, breastfeeding should be discontinued if the mother is treated.
Patients with known HIV infection or viral hepatitis.
Patients with Dihydropyrimidine dehydrogenase (DPD) deficiency.

Sites / Locations

Yale Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemo with concomitant Capecitabine and KD018

Arm Description

Patients will receive a course of chemo-radiation with concomitant Capecitabine and KD018, and to compare this to the toxicity seen in patients treated with Capecitabine and radiation therapy alone, in patients with T3-T4 and N0-N2, M0 rectal cancer.

Outcomes

Primary Outcome Measures

Grade 3-4 Toxicity Rate

Grade 3-4 toxicity rate will be described as greatest toxicity per patient/total patients evaluable for toxicity +/- 95% confidence interval.

pCR Rate

pCR (CR = Complete Response) rate will be defined as number of patients with pathologic complete response divided by number of patients treated (pCR IIT) and divided by those undergoing surgical resection (pCR actual) +/- 95% confidence interval.

Secondary Outcome Measures

Full Information

NCT ID

NCT02178644

First Posted

June 26, 2014

Last Updated

October 2, 2020

Sponsor

Yale University

1. Study Identification

Unique Protocol Identification Number

NCT02178644

Brief Title

Pilot Trial of KD018 With Neo-Adjuvant Concurrent Chemo-Radiation Therapy in Patients With Locally Advanced Rectal Cancer

Official Title

Pilot Trial of KD018 With Neo-Adjuvant Concurrent Chemo-Radiation Therapy in Patients With Locally Advanced Rectal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

July 2014 (undefined)

Primary Completion Date

September 20, 2019 (Actual)

Study Completion Date

September 20, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This pilot study focuses on KD018 and will investigate the effect of this agent on reducing the Gastrointestinal (GI) toxicity associated with combined modality therapy of locally-advanced rectal cancer.

Detailed Description

This pilot study focuses on KD018, a standardized and well-characterized Chinese herbal medicine, and will investigate the effect of this agent on reducing the GI toxicity associated with combined modality therapy of locally-advanced rectal cancer. In this study, KD018 will be administered concomitantly with Capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting, with the hypothesis that KD018 will reduce the gastrointestinal side effects, namely diarrhea, secondary to treatment with Capecitabine plus external beam radiation therapy (EBRT). The primary endpoint of the study is to investigate the grade 3-4 toxicity rate associated with a course of chemo-radiation with concomitant Capecitabine and KD018, and to compare this to the toxicity seen in patients treated with Capecitabine and radiation therapy alone, in patients with T3-T4 and N0-N2, M0 rectal cancer. Secondary objectives include the assessment of radiographic response to therapy (using pelvic MRI) and assessment of the pathologic CR rate by examination of the pathologic specimen. In addition, we will perform an analysis of plasma levels of pro-inflammatory cytokines and chemokines. This trial is designed to accrue approximately 24 patients over the course of 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chemo with concomitant Capecitabine and KD018

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Chemo with concomitant Capecitabine and KD018

Other Intervention Name(s)

KD018, Capecitabine, Neo-Adjuvant Concurrent Chemo-Radiation Therapy

Intervention Description

Primary Outcome Measure Information:

Title

Grade 3-4 Toxicity Rate

Description

Grade 3-4 toxicity rate will be described as greatest toxicity per patient/total patients evaluable for toxicity +/- 95% confidence interval.

Time Frame

Up to 10 Months

Title

pCR Rate

Description

Time Frame

Up to 10 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have histologically confirmed T3-T4 and N0-N2, M0 adenocarcinoma of the rectum with the inferior margin within 16 cm from the anal verge. Patients must have had a Transrectal ultrasound (TRUS)/endoscopic ultrasound (TEUS) staging within two months prior to treatment start. Patients must have had a pelvic MRI within 28 days prior to the initiation of treatment. Patient must have the ability to swallow multiple capsules. Women of child bearing potential between the ages of 18 and 60 years of age must have a negative urine pregnancy test prior to undergoing simulation in preparation for radiation therapy to the pelvis. ECOG performance status of 0 to 1 within 28 days prior to initiation of treatment. Patients must have normal organ and marrow function as defined below. All laboratory values must be obtained within 14 days prior to initiation of treatment: absolute neutrophil count >= 1,500/mcL platelets >= 100,000/mcL hemoglobin >= 8.0 g/ dL serum bilirubin < 1.5 times the upper limit of of normal (ULN) serum AST, ALT < 2.5 times ULN serum Creatinine ≤ 1.5 times ULN The effects of radiation on the developing human fetus are known to be teratogenic. For this reason, all women and sexually active men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Patients must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria History of clinically significant Crohn's disease or inflammatory bowel disease (IBD). Active collagen vascular disease. History of previous abdominal or pelvic radiation therapy. History of previous systemic chemotherapy unless given curatively for other malignancy now > 5 years without evidence of recurrence. Patients with suspected or confirmed poor compliance, mental instability, or prior or current alcohol or drug abuse deemed by the investigator to be likely to affect their ability to sign the informed consent, or undergo study procedures will be excluded. Pregnant women are excluded from this study because radiation has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with either KD018 or Capecitabine, breastfeeding should be discontinued if the mother is treated. Patients with known HIV infection or viral hepatitis. Patients with Dihydropyrimidine dehydrogenase (DPD) deficiency.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Susan A Higgins, M.D., M.S.

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yale Cancer Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06519

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Pilot Trial of KD018 With Neo-Adjuvant Concurrent Chemo-Radiation Therapy in Patients With Locally Advanced Rectal Cancer

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