Chemoradiation or Brachytherapy for Rectal Cancer

NCT02017704 | Completed Phase 2 Results

• 2 other identifiers: J1360NA_00082167
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief Summary

This research is being done to compare the effectiveness of high dose endorectal brachytherapy (END-HDR) and the standard treatment option of chemoradiation with Capecitabine in the treatment of cancer of the lowest part of the bowel (rectum).

Conditions

Rectal Cancer

Keywords

Endorectal Brachytherapy Radiation Therapy; Intensity Modulated Radiation Therapy and Capecitabine

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Pathologic Complete Response

  Pathologic complete response rate is reported as the number of patients who achieve pathologic complete response after the treatment for each arm. As per the NCCN guidelines, pathologic response is graded by the system recommended by the AJCC Cancer Staging Manual and CAP guidelines: * Complete response - no remaining viable cancer cells * Moderate response - only small clusters/single cancer cells remain * Minimal response - residual cancer remaining, but with predominant fibrosis * Poor response - minimal/no tumor kills, extensive residual cancer

  Up to 60 months

Secondary Outcomes (6)

• Number of Participants With Grade 3 or Higher Adverse Events

  Up to 60 months

• Change in EORTC QLQ-C30 Global Health Status Score

  baseline, preop, postop, and at follow ups Y1-5

• Time to Death

  Up to 60 months

• Time to Distant Metastases Free Survival

  Up to 60 months

• Time to Progression Free Survival

  Up to 60 months

Study Arms (2)

IMRT and Capecitabine

ACTIVE COMPARATOR

Patients will receive IMRT along with capecitabine. External radiotherapy will be based on contouring guidelines from the RTOG atlas and Radiation Therapy Oncology Group (RTOG 0822) with some modifications Followed by: * Oxaliplatin: 85 mg/m² in 500ml glucose 5% solution, 2-h infusion * 5-Fluorouracil (5-FU) bolus 400mg/m² following the oxaliplatin/FA infusions * 5-FU continuous infusion 2400 mg/m², 46-h infusion following the 5-FU bolus Cycle length: 14 days (2 weeks) Duration of treatment: 12 cycles Then: Surgical Resection

Drug: capecitabine and IMRT (if randomized to this arm); Radiation: IMRT (intensity modulated radiation therapy); Drug: FOLFOX6; Procedure: Surgery

Endo-HDR

EXPERIMENTAL

Patients will be treated with a daily dose of 6.5 Gy over four consecutive days for a total of 26 Gy Followed by: * Oxaliplatin: 85 mg/m² in 500ml glucose 5% solution, 2-h infusion * 5-Fluorouracil (5-FU) bolus 400mg/m² following the oxaliplatin/FA infusions * 5-FU continuous infusion 2400 mg/m², 46-h infusion following the 5-FU bolus Cycle length: 14 days (2 weeks) Duration of treatment: 12 cycles Then: Surgical Resection

Radiation: Endo-HDR (if randomized to this arm); Drug: FOLFOX6; Procedure: Surgery

Interventions

Endo-HDR (if randomized to this arm) RADIATION

Patients will be treated with a daily dose of 6.5 Gy over four consecutive days for a total of 26 Gy

Endo-HDR

capecitabine and IMRT (if randomized to this arm) DRUG

Capecitabine shall be delivered at 825mg/m2 BID during IMRT radiotherapy

Also known as: Xeloda

IMRT and Capecitabine

IMRT (intensity modulated radiation therapy) RADIATION

Patients will receive IMRT along with capecitabine. External radiotherapy will be based on contouring guidelines from the RTOG atlas and Radiation Therapy Oncology Group (RTOG 0822) with some modifications

IMRT and Capecitabine

FOLFOX6 DRUG

* Oxaliplatin - 85 mg/m² in 500ml glucose 5% solution, 2-h infusion * Leucovorin - bolus 400mg/m² following the oxaliplatin/FA infusions * 5 Fluorouracil (5FU) - 2400 mg/m², 46-h infusion following the 5-FU bolus An outpatient, 46 hour continuous IV infusion provided by a home IV infusion company. The 5FU is delivered by a small pump worn in a fanny pack around the waist. The home IV infusion company will arrange your disconnect at the end of the infusion.

Also known as: Oxaliplatin, Leucovorin, 5 Fluorouracil

Endo-HDR; IMRT and Capecitabine

Surgery PROCEDURE

After the patient has been identified as a candidate for the trial, the surgeon will assess the patient and will determine: Exact height and location of tumor with regards to the anal margin as measured by a rigid or flexible proctoscope and/or digital exam. Mobility of tumor as assessed if possible by rectal exam Type of surgical procedure: Abdominoperineal resection vs. sphincter saving procedures, which will include colo-anal with mucosectomy vs. stapled anastomosis.

Endo-HDR; IMRT and Capecitabine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed adenocarcinoma of the rectum
• Appropriate tumor staging and location
• Patients should be suitable candidates for surgery and chemotherapy
• ECOG/WHO performance status 0-1
• Patients must be 18 years or older
• No previous history of pelvic radiation
• Patients must have acceptable organ and marrow function
• Non pregnant, non-breast feeding females under active contraception
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Evidence of distant metastatic disease
• Evidence of sphincter invasion on MRI
• Prior history of radiation to the pelvis
• Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, DCIS, or other cancer from which the patient has been disease free for at least 3 years
• Presence of multiple small bowel loops trapped within the immediate tumor bed (post hysterectomy or prostatectomy).
• Use of any investigational agent within the 4 weeks preceding enrollment
• Previous exposure to chemotherapy for rectal cancer
• Uncontrolled intercurrent illness including but not limited to, ongoing or active infections (or infections requiring systemic treatment), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and breastfeeding women are excluded, as well as women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control (hormonal or barrier method of birth control; abstinence) to avoid pregnancy for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately.
• Women who are not post-menopausal and have a positive urine or serum pregnancy test or refuse to take a pregnancy test.
• Contraindication for safe MRI, implants, or other conditions that interfere with imaging required for the study (e.g., pacemaker or non-MRI compatible hip prostheses). Note: Subjects with bilateral hip implants are not eligible for the study. Subjects with a unilateral hip implant may be eligible assuming the implant is MRI compatible and does not present artifact on MRI in the areas of interest.
• Subject is pacemaker dependent.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Elekta Limited: collaborator

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33607, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

The SKCCC at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Beth Israel Hospital

New York, New York, 10003, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Radiotherapy, Intensity-Modulated; Folfox protocol; Oxaliplatin; Leucovorin; Fluorouracil; Surgical Procedures, Operative

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)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Amol Narang, MD
• Organization: SKCCC @ Johns Hopkins Medicine

anarang2@jhmi.edu

410-955-7390

Study Officials

• Amol K Narang, M.D.

  The SKCCC at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 23, 2013
• Study Start: June 12, 2014
• Primary Completion: September 30, 2021
• Study Completion: January 31, 2023
• Last Updated: October 17, 2023
• Results First Posted: February 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)