Organ Preservation Program Using Short-Course Radiation & FOLFOXIRI in Rectal Cancer

NCT04380337 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB-56027COR0019
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the research is to evaluate whether both chemotherapy and radiotherapy can lead to higher rates of clinical complete response leading to organ preservation in human subjects with cancer. The objective is to learn if this treatment approach may safely be used as an alternative to the standard treatment for rectal cancer and to know the quality-of-life in these patients.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Complete Response (cCR)

  Proportion of patients who achieve a clinical complete response following therapy, expressed as a number and proportion without dispersion.

  8 (+/-4 ) weeks following completion of RT and chemotherapy, an average of 9 months

Secondary Outcomes (5)

• Number of Participants With Toxicity

  8 (+/- 4) weeks following completion of RT and chemotherapy, an average of 3 months

• Local Regrowth Rate

  22 (+/- 2) months following completion of RT and chemotherapy, an average of 24 months (2 years)

• Disease Free Survival (DFS)

  22 (+/- 2) months following completion of RT and chemotherapy, an average of 24 months (2 years)

• Colostomy-free Survival

  22 (+/- 2) months following completion of RT and chemotherapy, an average of 24 months (2 years)

• Overall Survival (OS)

  27 (+/- 4) months following completion of RT and chemotherapy, an average of 2.25 years

Study Arms (1)

Radiation/FOLFOXIRI

EXPERIMENTAL

Treatment will comprise 6 daily fractions of radiotherapy at 5 Gy per fraction followed by 4 months of FOLFOXIRI. Patients who have performance status or conditions that may preclude use of FOLFOXIRI may be treated with FOLFOX or XELOX. Those who achieve a clinical complete response will be considered for organ preservation approach. All other patients will receive standard of care total mesorectal excision (TME).

Drug: FOLFOXIRI; Drug: FOLFOX regimen; Drug: XELOX; Radiation: IMRT

Interventions

FOLFOXIRI DRUG

Chemotherapy regimen of Oxaliplatin 85mg/m2 , Leucovorin 400 mg/m2 , Irinotecan 165mg/m2 , 5-Fluorouracil

Radiation/FOLFOXIRI

FOLFOX regimen DRUG

Chemotherapy regimen of Oxaliplatin 85mg/m2, Leucovorin 400 mg/m2, 5-Fluorouracil 2400mg/m2

Radiation/FOLFOXIRI

XELOX DRUG

Chemotherapy regimen of Oxaliplatin 130 mg/m2, Capecitabine 1000mg/m2

Radiation/FOLFOXIRI

IMRT RADIATION

Radiotherapy (5 Gy x 5 fractions) with an additional boost fraction (5 Gy x 1 fraction) delivered sequentially

Also known as: Intensity-modulated radiotherapy (IMRT)

Radiation/FOLFOXIRI

Eligibility Criteria

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

You may qualify if:

• \. Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of rectum requiring total mesorectal excision as deemed by multidisciplinary evaluation
• At least 18 years of age
• For women of childbearing potential or who are not postmenopausal (see Appendix B for Definition of Menopausal Status), a negative urine or serum pregnancy test must be done. Also, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for up to 4 weeks following the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• ECOG 0, 1, or 2
• Ability to understand and the willingness to personally sign the written IRB approved informed consent document.
• Patients must have acceptable organ and marrow function as defined below:
• Absolute neutrophil count (ANC) \>1,500/uL
• Hg \> 8.0 g/dL; if blood transfusion is performed for achieving adequate hemoglobin level, the level should stay above goal for at least 1 week after transfusion
• Platelets \>100,000/uL
• Total bilirubin \<1.5X normal institutional limits
• aspartate aminotransferase (AST) (SGOT) / alanine aminotransferase (ALT)(SGPT) \< 3X upper limit of normal
• Creatinine \<1.5X upper limit of normal or creatinine clearance (CrCL)\>50 by Cockcroft-Gault
• Clinical stage \>T2N0 or low T2N0 rectal cancer (AJCC, 8th ed.) including no metastases based on the following diagnostic workup:
• General history and physical examination with DRE (if deemed appropriate by treating physician) within 45 days prior to enrollment
• Sigmoidoscopy within 90 days prior to enrollment

You may not qualify if:

• Prior pelvic RT or chemotherapy for rectal cancer.
• Upper T2N0 rectal cancers eligible for sphincter-preservation surgery
• Use of other investigational agents.
• Ongoing or active infections requiring systemic antibiotic treatment or uncontrolled intercurrent illness including but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any concurrent malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. Patients with any previous malignancy without evidence of disease for \>3 years will be allowed to enter the trial.
• Known hypersensitivity to 5-FU compounds.
• Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study are excluded. (This applies to women who have experienced menarche and have not undergone successful surgical sterilization or are not postmenopausal).
• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, known HIV-positive patients with detectable viral loads and/or receiving combination anti-retroviral therapy are excluded from the study.
• \- 8.Primary unresectable rectal cancer (tumor invading adjacent organs and en bloc resection will not achieve negative margins).

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94304, United States

Location

Related Publications (1)

• Brown E, Fisher GA Jr, Shelton A, Chang DT, Pollom E. Advancing clinical trial equity through integration of telehealth and decentralized treatment. JNCI Cancer Spectr. 2024 Jul 1;8(4):pkae050. doi: 10.1093/jncics/pkae050.

  PMID: 38902952 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

FOLFOXIRI protocol; Folfox protocol; XELOX; Radiotherapy, Intensity-Modulated

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)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Erqi Pollom
• Organization: Stanford University

erqiliu@stanford.edu

650-498-0484

Study Officials

• Erqi L Pollom

  Stanford Universiy

  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: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiation Oncology

Study Record Dates

• First Submitted: May 5, 2020
• First Posted: May 8, 2020
• Study Start: May 21, 2020
• Primary Completion: January 17, 2024
• Study Completion: January 17, 2024
• Last Updated: February 25, 2025
• Results First Posted: February 25, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)