Status and phase
Conditions
Treatments
About
This is an open-label Phase II trial that will investigate the use of neoadjuvant CAPEOX chemotherapy with Atezolizumab followed by surgery and adjuvant chemotherapy for patients with localized resectable pMMR adenocarcinoma of the colon with a target accrual of 30 patients.
The investigators will explore if appropriately timed neoadjuvant CAPEOX with anti-PD-L1 mAb (Atezolizumab) can be administered safely and feasibly for 12 weeks, and that this combination will lead to improved clinical response associated with enhanced numbers of immune cells in surgically resected colon tumors.
Participants will receive 4 cycles of atezolizumab in combination with 4 cycles of CAPEOX (atezolizumab will be administered prior to chemotherapy) before standard of care surgical resection. Each cycle of neoadjuvant therapy is 3 weeks. Following surgery, participants still considered to be at high-risk of recurrence (per NCCN guidelines) will receive further adjuvant chemotherapy (mFOLFOX6 or CAPEOX),for 6 and 4 cycles respectively (for a total of 12 weeks), based on the discretion of the treating oncologist/investigator.
Participants will be followed up for an EFFICACY follow-up phase every 2 months during the first 6 months after surgery (months 1, 3, 6) and thereafter participants will enter a SURVIVAL follow-up phase and will be seen every 6 months starting at month 12 until month 36. During this the efficacy and survival follow up visits blood samples will be obtained for purposes of obtaining circulating DNA and stool and optional blood samples for storage for future exploratory analysis. Additionally, during these follow up visits, participants will be asked to complete quality of life questionnaires
Full description
Once participants' eligibility has been confirmed, and participants have been registered in the study, the participants will receive immunotherapy treatment with Atezolizumab, followed by administration of CAPEOX chemotherapy for a total of four cycles. Each cycle is 3 weeks; a total of four cycles will be administered and must be completed within 15 weeks. Participants will receive growth factor support at the treating physician's discretion.
Participants will receive 4 cycles (one cycle every 3 weeks) of Atezolizumab along with 4 cycles (one cycle every3 weeks) of CAPEOX before surgery. Atezolizumab will be initiated starting with Cycle 1 Day 1 (during first chemotherapy session). Trial intervention(s) should begin on the day of enrollment (the process of registering or entering a patient into a clinical trial) or as close as possible to the date on which intervention is allocated/assigned.
Following surgery, the treating investigator will monitor and determine the risk of disease recurrence (the risk of the cancer coming back) after surgery. In addition, investigators will collect a series of blood sample collections called ctDNA monitoring assay. This blood test will be specific to each participant, and it may indicate if more chemotherapy is needed after surgery. In case participants' ctDNA test comes back as positive (+) at any point, the investigators will discuss with participant about the possibility of receiving further chemotherapy for an additional 12 weeks. This chemotherapy regimen will be either mFOLFOX6 (every 2 weeks for a total of 6 cycles= 12 weeks) or CAPEOX chemotherapy (every 3 weeks for a total of 4 cycles= 12 weeks). Toxicities (undesirable effects of medications) for Atezolizumab and CAPEOX will be continuously monitored to make sure their side effects are in line with prior experience of their use, individually or combined.
Re-Staging Staging is a way to describe a cancer. The cancer's stage tells the investigators where a cancer is located and its size, how far it has grown into nearby tissues, and if it has spread to nearby lymph nodes (a small bean-shaped structure that is part of the body's immune system) or other parts of the body.
For this study, the investigators will order for participants to have a Computerized Tomography (CT), a series of X-ray images taken from different angles, or a Magnetic Resonance Imaging (MRI), a medical imaging technique that uses a magnetic field and computer-generated radio waves to create detailed images of the organs and tissues in the body, done before any intervention, with the purpose of staging the cancer, determining if it is removable by surgery.
Restaging with the same method of imaging used to meet initial eligibility requirements, including either contrast-enhanced CT or MRI (for patients with an intravenous contrast allergy) must be performed 2-4 weeks following completion of chemotherapy. All re-staging imaging will be centrally reviewed for assessment of resectability (to determine if the cancer can be removed).
SURGERY After participants have recovered sufficiently from any adverse effects of neoadjuvant chemotherapy and still have removable cancer on re-staging, the investigator should proceed to surgery at the participating site within 8 weeks following completion of chemotherapy.
ADJUVANT CHEMOTHERAPY Following surgery, the treating investigator will monitor and determine the risk of disease recurrence (the risk of the cancer coming back) after surgery. In addition, the investigators will collect a series of blood sample collections called ctDNA monitoring assay. This blood test will be specific to each participant, and it may indicate if more chemotherapy is needed after surgery. In case participants' ctDNA test comes back as positive (+) at any point, the investigator will discuss with participants about the possibility of receiving further chemotherapy for an additional 12 weeks. This chemotherapy regimen will be either mFOLFOX6 (every 2 weeks for a total of 6 cycles= 12 weeks) or CAPEOX chemotherapy (every 3 weeks for a total of 4 cycles= 12 weeks).
FOLLOW UP VISITS Participants will be followed up for an efficacy follow-up phase every 2 months during the first 6 months after surgery (months 1, 3, 6), and thereafter they will enter a survival follow-up phase and will be seen every 6 months starting at month 12 until month 36. During these visits the investigators are going to monitor participants blood for ctDNA analysis and whole blood samples (for future research analysis), vital status updates, quality of life questionnaires, routine laboratory assessments, and standard of care imaging.
All screening evaluations must be completed and reviewed to confirm that potential participants meet all eligibility criteria.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Signed Informed Consent Form
Age >18 years at time of signing Informed Consent Form
Ability to comply with the study protocol
MSS or pMMR tumor determined by local CLIA-certified PCR or IHC testing respectively.
Histologically or cytologically confirmed resectable non-metastatic adenocarcinoma of the colon (stages I-III)
The distal extent of the tumor must be ≥12 cm from the anal verge on pre-surgical endoscopy and/or imaging (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation). If the patient did not undergo a pre-surgical endoscopy, then the distal extent of the tumor must be ≥12 cm from the anal verge as determined by surgical examination or pre-operative imaging.
Availability of a representative tumor specimen (preop biopsy or surgical tissue specimen) for ctDNA assay design from tumor sample and for exploratory biomarker research determination.
One or more of the following high-risk features:
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN
Serum creatinine ≤1.5 x ULN or Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
Serum albumin ≥ 25 g/L (2.5 g/dL)
For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the final dose of atezolizumab and for 6 months following any of the adjuvant chemotherapy regimens (if applicable) after the final dose of mFOLFOX6 or CAPEOX.Women must refrain from donating eggs during this same period.
A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for 5 months after the final dose of any chemotherapy regimen. Men must refrain from donating sperm during this same period.
With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 5 months after any of the chemotherapy regimens to avoid exposing the embryo.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
Exclusion criteria
Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
Rash must cover < 10% of body surface area
Disease is well controlled at baseline and requires only low-potency topical corticosteroids
There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
Primary purpose
Allocation
Interventional model
Masking
30 participants in 1 patient group
Loading...
Central trial contact
Hector J Garcia-Chavez, MD
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal