Organ Preservation With Active Surveillance After Chemoradiation in Rectal Cancer (OPTION)
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Recruiting
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 120
- Locations
- 2
- Primary Endpoint
- Local tumor regrowth rate
Study Overview
Brief Summary
This pilot trial studies how well active surveillance and chemotherapy before surgery work in treating participants with stage II-III rectal cancer. Active surveillance involves monitoring participants for additional tumor growth after receiving cancer treatment. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether deferring surgery after active surveillance and chemotherapy will work better in treating participants with stage II-III rectal cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To quantify the rates of organ preservation and tumor regrowth with non-operative management of locally advanced rectal cancer in patients achieving a clinical complete response (cCR).
SECONDARY OBJECTIVES:
I. To correlate clinical, radiographic, and pathologic findings after neoadjuvant therapy for rectal cancer.
II. To determine the impact of active surveillance with deferral of surgery on oncologic outcomes.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed diagnosis of rectal adenocarcinoma
- •Eligible for curative resection of rectal adenocarcinoma
- •Rectal tumor location =< 12 cm from the anal verge as determined by endoscopy or magnetic resonance imaging (MRI) (if endoscopy report is not available or deemed inadequate my treating oncologist)
- •Nodal involvement confined to the radiation field
- •Radiologically measurable or clinically evaluable disease as defined in the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0, 1 or 2
- •Clinical Stage: Stage II and III. N2 disease is to be estimated as four or more lymph nodes that are >= 10 mm. Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon including digital rectal exam (DRE), computed tomography (CT) or positron emission tomography (PET)/CT scan of the chest/abdomen/pelvis and a pelvic MRI. If a pelvic MRI is performed, it is acceptable to perform CT of the chest/abdomen, omitting CT imaging of the pelvis. PET/CT is optional.
- •No known contraindication to standard (fluoropyrimidine-based) pelvic chemoradiation (e.g. dihydropyrimidine dehydrogenase [DPD] deficiency)
- •Patient of child-bearing potential is willing to employ adequate contraception during treatment and after treatment, as directed by treating clinical team
- •Willing to provide written informed consent
- •Willing to return to enrolling medical site for all study assessments
Exclusion Criteria
- •Diagnosis of inflammatory bowel disease (IBD)
- •Diagnosis of MSI-H colorectal cancer at time of consent
- •Recurrent rectal cancer
- •Tumor is causing symptomatic bowel obstruction (patients who have diverting ostomy are eligible)
- •Any prior pelvic radiation
- •Other invasive malignancy undergoing active treatment. Patients receiving prior treatment that precludes standard chemoradiation or ability to receive consolidation/adjuvant chemotherapy will be excluded from survival analyses
- •Patients unwilling or unable to undergo pelvic MRI
Arms & Interventions
Group II (active surveillance)
Participants who have achieved clinical complete response receive active surveillance and consolidated chemotherapy for up to 4 months in the absence of disease progression or unacceptable toxicity. Participants with incomplete response or regrowth of tumor, undergo surgical resection as in Group I.
Intervention: Questionnaire Administration (Other)
Group II (active surveillance)
Participants who have achieved clinical complete response receive active surveillance and consolidated chemotherapy for up to 4 months in the absence of disease progression or unacceptable toxicity. Participants with incomplete response or regrowth of tumor, undergo surgical resection as in Group I.
Intervention: Resection of Rectum (Procedure)
Group II (active surveillance)
Participants who have achieved clinical complete response receive active surveillance and consolidated chemotherapy for up to 4 months in the absence of disease progression or unacceptable toxicity. Participants with incomplete response or regrowth of tumor, undergo surgical resection as in Group I.
Intervention: Patient Observation (Other)
Group I (surgical resection)
Participants who have achieved clinical complete response undergo standard surgical resection.
Intervention: Questionnaire Administration (Other)
Group I (surgical resection)
Participants who have achieved clinical complete response undergo standard surgical resection.
Intervention: Resection of Rectum (Procedure)
Group II (active surveillance)
Participants who have achieved clinical complete response receive active surveillance and consolidated chemotherapy for up to 4 months in the absence of disease progression or unacceptable toxicity. Participants with incomplete response or regrowth of tumor, undergo surgical resection as in Group I.
Intervention: Chemotherapy (Drug)
Outcomes
Primary Outcomes
Local tumor regrowth rate
Time Frame: At 12 months
The study will estimate local tumor regrowth rate at 12 months and the corresponding 95% confidence interval (95% CI). The exact confidence interval will be computed when observed number of events is limited. The 12-month organ preservation rate corresponds to the proportion of patients alive and not having surgery within 12 months. The study will use Kaplan-Meier methods to estimate probability of local tumor regrowth at 12 months for all patients and for deferral patients respectively.
Time to surgery or death
Time Frame: Up to 12 months
The study will use Kaplan-Meier methods to estimate probability for deferral patients respectively.
Overall organ preservation rate
Time Frame: At 12 months
The study will estimate overall organ preservation rate at 12 months and the corresponding 95% confidence interval (95% CI). The exact confidence interval will be computed when observed number of events is limited. The 12-month organ preservation rate corresponds to the proportion of patients alive and not having surgery within 12 months. The study will use Kaplan-Meier methods to estimate probability of overall organ preservation at 12 months at 12 months for all patients and for deferral patients respectively.
Secondary Outcomes
- Surgical success rates(Up to 5 years)
- Overall survival (OS)(Up to 5 years)
- Regression-free survival (RFS)(Up to 5 years)
- Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0(Up to 5 years)
- Decision quality assessment determined by European Organization for Treatment and Research of Cancer Quality of Life Questionnaire (EORTC-QLQ30+CR29)(Up to 3 years)
- Pathologic Findings(Up to 5 years)
- Radiographic Findings(Up to 5 years)