This study is currently recruiting participants.
Number
001691-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Children;Fetuses;Neonates
Keywords
nivolumab; Ipilimumab; Immune Checkpoint Blockade; mismatch repair
Recruitment Keyword(s)
None
Condition(s)
Colorectal Cancer; gastroesophageal cancer
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Drug: nivolumab Drug: ipilimumab
Supporting Site
National Cancer Institute
People with colorectal cancer (CRC) or gastroesophageal cancer (GEC) must often have major surgery to remove tumors from the esophagus, stomach, colon, or rectum. These surgeries can have adverse effects on their quality of life. Researchers want to know if one or two approved drugs (nivolumab with or without ipilimumab) can help people with CRC or GEC delay or avoid surgery.
Objective:
To test 1 or 2 drugs in people with CRC or GEC.
Eligibility:
People aged 18 years and older with CRC or GEC. People with GEC must also have changes in a particular gene.
Design:
Participants will visit the clinic about 15 times over the first 2 years. Each visit will last 4 to 8 hours.
Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans. Small samples of tissue will be collected from their upper or lower digestive tract where the tumor is located.
Both ipilimumab and nivolumab are administered through a tube attached to a needle inserted into a vein in the arm. Some participants will receive both drugs. Some will receive only nivolumab. Treatment will be given once every 3 weeks for up to 8 cycles up to (24 weeks).
Participants will be evaluated every 6 weeks. Those who are responding well will continue with the drug treatments. If their disease progresses, they will go to surgery.
After treatment ends, participants will have follow-up visits every 6 months for up to 5 years.
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INCLUSION CRITERIA: -Participants must have biopsy-proven stage I-III colorectal cancer (CRC) [any MMR or Tumor Mutational Burden (TMB) status] or stage I-III gastroesophageal cancer (GEC) (MMR deficient only). -Participants with known mismatch repair protein expression by immunohistochemical staining and/ or known next-generation sequencing report of tumor mutational burden and/or microsatellite status. Note: For participants that come to NIH with an equivocal MMR status, next-generation sequencing (NGS) by TSO500 will be done at NIH. -More than four weeks must have elapsed since completion of any prior systemic therapy or radiotherapy at the time of enrollment. Participants are permitted to have undergone prior treatment with systemic chemotherapy (e.g. FOLFOX, FOLFIRI, FLOT) and/or radiotherapy. Note: Participant may have undergone minor surgical procedures within the four weeks prior to enrollment, if related major organ toxicities have recovered to <= grade 1. -Participants must have endoscopically evaluable disease. -Age >=18 years. -ECOG performance status =<1. -Participants must have adequate organ and marrow function as defined below: --White Blood Cell (WBC), >=3,000/mm^3 --Hemoglobin >8.0 d/dL, (transfusion permitted) --platelets, >=100,000/mm^3 --total bilirubin, < 1.5 mg/dL (except in participants with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dL) --AST(SGOT)/ALT(SGPT), 5.0 X institutional upper limit of normal --serum creatinine, < 1.6 mg/dL -No pre-existing autoimmune or infectious conditions for which treatment with immune checkpoint blockade is contraindicated. -Serology --Seronegative for HIV antibody. --Seronegative for hepatitis B surface antigen and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative -Must have a negative pregnancy test. -Women of childbearing potential must be willing to must agree to use adequate contraception (surgical sterilization, partner vasectomy, hormonal or barrier method of birth control; abstinence) from the time of enrollment through 3 months after ipilimumab or for 5 months after nivolumab, whichever is later. -Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 months after ipilimumab or for 5 months nivolumab, whichever is later. -Ability of participant to understand and the willingness to sign a written informed consent document. -Participants with MMR proficient colon tumors must have extenuating circumstances that make surgical treatment an unacceptable option. This must be documented in the medical record. Some examples: --Religious or strong personal objections --Prior colorectal surgery, such that another resection could lead to short gut, permanent stoma or detriment to quality of life -Participant must be co-enrolled on protocol 03-C-0277 EXCLUSION CRITERIA: -Participants who are receiving any other investigational agents. -Previous treatment with checkpoint inhibitors (anti-CTLA-4, anti-PD-1 or anti-PD-L1 antibodies) for the primary tumor in question. -History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and ipilimumab or other agents used in study. -Concomitant medications, such as steroids or other immunosuppressive agents, that have the potential to affect the activity of the study agents. -Any active or uncompensated major medical illness that would preclude major intraabdominal surgery. -Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) or any immune disorder that would be a contraindication to ICB treatment. -Concurrent opportunistic infections -Tumor is causing symptomatic bowel obstruction (participants with a diverting ostomy are eligible). -History of significant autoimmune adverse events due to administration of anti-PD-1, anti-PD L1 or anti-CTLA-4 antibodies when given for prior indication. -Participants who are medically unfit to undergo major abdominal surgery. -Participants with tumors that are unable to be endoscopically evaluated. -Uncontrolled intercurrent illness that would limit compliance with study requirements.
-Participants must have biopsy-proven stage I-III colorectal cancer (CRC) [any MMR or Tumor Mutational Burden (TMB) status] or stage I-III gastroesophageal cancer (GEC) (MMR deficient only).
-Participants with known mismatch repair protein expression by immunohistochemical staining and/ or known next-generation sequencing report of tumor mutational burden and/or microsatellite status. Note: For participants that come to NIH with an equivocal MMR status, next-generation sequencing (NGS) by TSO500 will be done at NIH.
-More than four weeks must have elapsed since completion of any prior systemic therapy or radiotherapy at the time of enrollment. Participants are permitted to have undergone prior treatment with systemic chemotherapy (e.g. FOLFOX, FOLFIRI, FLOT) and/or radiotherapy. Note: Participant may have undergone minor surgical procedures within the four weeks prior to enrollment, if related major organ toxicities have recovered to <= grade 1.
-Participants must have endoscopically evaluable disease.
-Age >=18 years.
-ECOG performance status =<1.
-Participants must have adequate organ and marrow function as defined below:
--White Blood Cell (WBC), >=3,000/mm^3
--Hemoglobin >8.0 d/dL, (transfusion permitted)
--platelets, >=100,000/mm^3
--total bilirubin, < 1.5 mg/dL (except in participants with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dL)
--AST(SGOT)/ALT(SGPT), 5.0 X institutional upper limit of normal
--serum creatinine, < 1.6 mg/dL
-No pre-existing autoimmune or infectious conditions for which treatment with immune checkpoint blockade is contraindicated.
-Serology
--Seronegative for HIV antibody.
--Seronegative for hepatitis B surface antigen and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative
-Must have a negative pregnancy test.
-Women of childbearing potential must be willing to must agree to use adequate contraception (surgical sterilization, partner vasectomy, hormonal or barrier method of birth control; abstinence) from the time of enrollment through 3 months after ipilimumab or for 5 months after nivolumab, whichever is later.
-Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 3 months after ipilimumab or for 5 months nivolumab, whichever is later.
-Ability of participant to understand and the willingness to sign a written informed consent document.
-Participants with MMR proficient colon tumors must have extenuating circumstances that make surgical treatment an unacceptable option. This must be documented in the medical record. Some examples:
--Religious or strong personal objections
--Prior colorectal surgery, such that another resection could lead to short gut, permanent stoma or detriment to quality of life
-Participant must be co-enrolled on protocol 03-C-0277
EXCLUSION CRITERIA:
-Participants who are receiving any other investigational agents.
-Previous treatment with checkpoint inhibitors (anti-CTLA-4, anti-PD-1 or anti-PD-L1 antibodies) for the primary tumor in question.
-History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and ipilimumab or other agents used in study.
-Concomitant medications, such as steroids or other immunosuppressive agents, that have the potential to affect the activity of the study agents.
-Any active or uncompensated major medical illness that would preclude major intraabdominal surgery.
-Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) or any immune disorder that would be a contraindication to ICB treatment.
-Concurrent opportunistic infections
-Tumor is causing symptomatic bowel obstruction (participants with a diverting ostomy are eligible).
-History of significant autoimmune adverse events due to administration of anti-PD-1, anti-PD L1 or anti-CTLA-4 antibodies when given for prior indication.
-Participants who are medically unfit to undergo major abdominal surgery.
-Participants with tumors that are unable to be endoscopically evaluated.
-Uncontrolled intercurrent illness that would limit compliance with study requirements.
Principal Investigator
Referral Contact
For more information: