Clinical trial NCT03548961: Organ Preservation in Early Rectal Cancer Patients
Official title: GI-116: Phase II Study of Organ Preservation in Early Rectal Cancer Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
First posted: 2018-06-07
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single arm phase II study of neoadjuvant chemotherapy followed by local excision and post-operative chemoradiotherapy in patients with early stage, low rectal adenocarcinoma. After completion of pre-treatment tests/procedures (including pelvic MRI/ERUS; MRI is mandatory at baseline and other imaging is encouraged) and confirmation of eligibility, systemic therapy with FOLFOX will be administered for 12 weeks. 2 to 4 weeks after the chemotherapy, restaging of the primary tumor will be done to evaluate response to therapy (Pelvic MRI and /or sigmoidoscopy). Patients with disease progression or inadequate response to chemotherapy to allow local excision will continue with evaluation and treatment per the current standard of care (chemoradiation followed by TME). These patients will be considered failures for the primary endpoint of the study. Patients who respond to the neoadjuvant chemotherapy will proceed with local excision (open, TEMS or TAMIS), 6-12 weeks after the completion of neoadjuvant chemotherapy, followed by 5-FU based chemoradiotherapy 4-12 weeks after local excision. Patients with positive margins at the time of local excision will also be treated as per standard of care and will be considered as failures. Number of patients who can undergo successful local excision with this approach will define the success of the strategy. After chemoradiation therapy post local excision, patients will be followed closely every 3 months for the first 3 years and then every 2 months for the next 2 years (history/physical, CEA and pelvic MRI). Patients who are deemed failures for the primary end-point will be followed as per standard of care, off-study.


Eligibility criteria: Inclusion criteria

1. Histologically proven adenocarcinoma of the lower rectum (lower border ≤6 cm from anal verge as assessed by pelvic MRI).
2. Clinical stage T1N0, T2N0, T3N0; high risk T1 and low risk T3 stage patients are also allowed. Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, CT Chest/Abdomen/Pelvis or PET/CT along with Pelvic MRI and Endoscopic Rectal Ultrasound (ERUS). If a pelvic MRI is performed, it is acceptable to perform CT of the chest/abdomen, omitting CT imaging of the pelvis.
3. No prior therapy for rectal cancer
4. Age \> 18 years.
5. ECOG performance status 0 or 1
6. Patients must have normal organ and marrow function as defined below

   * Leukocytes \> 3,000/mcL
   * Absolute neutrophil count \> 1,500/mcL
   * Platelets \> 100,000/mcL
   * Total bilirubin \< 1.5 times ULN
   * AST/ALT (SGOT/SGPT) \< 3 times institutional normal limits
   * Creatinine \< 1.5 times ULN OR
   * Creatinine clearance \> 60 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal
7. Ability to understand and willingness to sign a written informed consent and HIPAA consent document

Exclusion Criteria:

1. Patients with contraindication to use FOLFOX chemotherapy and pelvic radiation.
2. Low risk T1 tumors that fulfill all of the following - size\<4 cm, lack of lymphovascular invasion and well differentiated histology, are excluded
3. High risk T3 tumors that fulfill any of the following - circumferential tumor, extension into mesorectal fascia \> 5mm, prediction of positive circumferential resection margin, are also excluded.
4. T4, node positive or advanced rectal adenocarcinoma. Node positivity defined as nodes greater than 1cm in short axis with loss of uniform cortex/fatty hilum
5. Patients receiving other investigational agents
6. Patients who have had chemotherapy (for other malignancies) within 3 years prior to registration
7. Patients with any prior pelvic radiation therapy
8. Prior malignancies requiring systemic therapy within the last 3 years (as prior therapy can increase toxicity of current chemo regimen, those patients should be excluded).
9. History of allergic reactions attributed to compound of similar chemical or biologic composition to the agents used in this study
10. 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.
11. Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic drugs. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
12. Pregnant or breast feeding.

Primary outcomes:
measure: number of patients whose tumor can be resected by local excision with negative margins
timeFrame: 3 months
Secondary outcomes:
measure: Number of patients with improved bowel function in patients treated with organ preserving approach for early stage low rectal cancer before and after therapy
timeFrame: 3 years
measure: Number of patients with improved sexual function treated with organ preserving approach for early stage low rectal cancer before and after therapy
timeFrame: 3 years
measure: Number of patients with improved health-related quality of life treated with organ preserving approach for early stage low rectal cancer before and after therapy
timeFrame: 3 years
measure: Overall survival (OS) of patients
timeFrame: 5 years
measure: Disease-free survival (DFS) of patients
timeFrame: 5 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
References: