Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum

NCT02641691 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: 201512140
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to look at how tumors responds to a short course of radiation (5 days) followed by 8 cycles of chemotherapy.

Conditions

Cancer of Rectum; Cancer of the Rectum; Neoplasm, Rectum; Rectal Cancer; Rectum Cancer; Rectum Neoplasms; Adenocarcinoma of the Rectum

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  * Criteria for complete clinical response: * No residual gross tumor at procto/sigmoidoscopy, or only erythematous scar or ulcer * No radiographic evidence of tumor on DRE * Substantial downsizing on MRI * No suspicious mesorectal lymph nodes on MRI * Negative biopsy from scar, ulcer, or former tumor site (if necessary according to surgeon's judgment) * Criteria for no significant clinical response: * Residual disease by DRE, endoscopy or MR. * Increase in primary tumor size upon clinical exam or imaging * Any new lesions

  1 year

Secondary Outcomes (8)

• Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire

  Baseline

• Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire

  Completion of chemoradiation (approximately 112 days)

• Prospective Patient Reported Outcomes as Measured by FACT-C Questionnaire

  10-14 months after chemoradiation (approximately 16-20 months)

• Number of Any Grade 3 or Higher Toxicities

  From start of radiation treatment through 30 days after completion of treatment (approximately 18 weeks)

• Number of Post Chemotherapy Grade 3 or Higher Toxicities

  Post-chemotherapy through 1 year follow-up (approximately 1 year and 4 months)

Study Arms (1)

Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU

EXPERIMENTAL

* Radiotherapy will consist of five fractions, delivered once daily, to a total dose of 25Gy at 5 Gy per fraction. * An optional concomitant boost may be delivered to the primary tumor of 1-2 Gy per day (30-35 Gy to tumor total). If a boost is given then the maximum allowed dose to small bowel is 25 Gy. * Chemotherapy should begin two weeks (9-12 working days) after completion of radiotherapy. * Oxaliplatin will be given intravenous (IV) over 2 hours on Day 1 every 14 days for a maximum of 8 cycles. * Leucovorin will be given IV over 2 hours on Day 1 every 14 days for a maximum of 8 cycles. * 5-FU bolus will given IV push on Day 1 every 14 days for a maximum of 8 cycles. * 5-FU infusion will be given continuous IV on Day 1 over 46 hours every 14 days for a maximum of 8 cycles * Alternatively, capecitabine/oxaliplatin (CAPE PO 1000 mg/m2 BID days 1-14 Q21 days, oxaliplatin IV 130 mg/m2 IV Q21 days on day 1) x 5 cycles over 15 weeks may be administered instead of FOLFOX

Radiation: Radiation; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil

Interventions

Radiation RADIATION

Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU

Oxaliplatin DRUG

Also known as: Eloxatin®

Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU

Leucovorin DRUG

Also known as: Wellcovorin, citrovorum factor, folinic acid, 5-formyl tetrahydrofolate

Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU

Fluorouracil DRUG

Also known as: 5-Fluorouracil, 5-FU

Arm 1: Radiation/Oxaliplatin/Leucovorin/5-FU

Eligibility Criteria

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

You may qualify if:

• Diagnosis of biopsy proven stage I-IIIB (cT1-3, N0-1, M0) adenocarcinoma of the rectum; staging must also be based on multidisciplinary evaluation including MRI and/or endorectal ultrasound
• Tumor ≤ 12 cm from anal verge as determined by MRI or endoscopy a
• ECOG performance status 0-2
• At least 18 years of age
• Adequate bone marrow function defined as:
• ANC \> 1,500 cells/mm3
• Hgb \> 8 g/dl
• platelets \>100,000 cells/mm3
• Women of childbearing potential and 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 must inform her treating physician immediately.
• Able to understand and willing to sign an IRB-approved written informed consent document.

You may not qualify if:

• No clinically detectable (MR, endoscopy or DRE) tumor present
• Prior radiation therapy, chemotherapy or extirpative surgery for rectal cancer.
• Any evidence of disease from another malignancy or history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix). Patients with history of prostate cancer treated without radiotherapy and no evidence of disease are eligible.
• Currently receiving any investigational agents.
• A history of allergic reaction attributed to compounds of similar chemical or biologic composition to 5FU, oxaliplatin, or leucovorin.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study entry.
• Known HIV-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with the study drugs. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Kim H, Pedersen K, Olsen JR, Mutch MG, Chin RI, Glasgow SC, Wise PE, Silviera ML, Tan BR, Wang-Gillam A, Lim KH, Suresh R, Amin M, Huang Y, Henke LE, Park H, Ciorba MA, Badiyan S, Parikh PJ, Roach MC, Hunt SR. Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial. Clin Colorectal Cancer. 2021 Sep;20(3):e185-e193. doi: 10.1016/j.clcc.2021.03.003. Epub 2021 Apr 7.

  PMID: 34001462 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiation; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Hyun Kim, M.D.
• Organization: Washington University School of Medicine

kim.hyun@wustl.edu

314-362-8502

Study Officials

• Hyun Kim, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: December 29, 2015
• Study Start: May 27, 2016
• Primary Completion: February 4, 2020
• Study Completion: March 29, 2020
• Last Updated: February 18, 2021
• Results First Posted: February 18, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)