Immunotherapy With Y90-RadioEmbolization for Metastatic Colorectal Cancer (iRE-C)

  • STATUS
    Recruiting
  • End date
    Oct 8, 2022
  • participants needed
    18
  • sponsor
    Chandrikha Chandrasekharan
Updated on 8 April 2022
cancer
tubal ligation
hysterectomy
serum pregnancy test
vegf
oophorectomy
metastasis
oxaliplatin
fluoropyrimidine
liver metastasis
EGFR
irinotecan
metastatic colorectal cancer
bevacizumab
durvalumab
vascular endothelial growth factor

Summary

This clinical trial will be conducted as a single-center, open-label, Phase I/2 trial to evaluate the feasibility and safety of Yttrium-90 radioembolization (Y90-RE) in combination with a fixed dose of of immunotherapy (durvalumab - 750 mg) in subjects with liver-predominant, metastatic colorectal cancer (mCRC), which is mismatch repair proficient/microsatellite stable (pMMR/MSS).

Description

The purpose of this clinical trial is to find out more about the side effects of immunotherapy with a form of radiation treatment for the cancer in the liver called Yttrium-90 RadioEmbolization (Y90-RE). An immunotherapy drug, durvalumab, will be given intravenously every 2 weeks. Investigators are studying what doses of durvalumab are safe for people in combination with this form of radiation treatment. Patients in this study will receive durvalumab, which is experimental and not approved by the U.S. Food and Drug Administration (FDA) for metastatic colorectal cancer. Microscopic radioactive particles (TheraSphere®) will be used for radioembolization to deliver the Y90 drug to the liver.

The number of doses of the immunotherapy drug (range: 2 to 5) will depend on the cohort patients are assigned to. There is no placebo. Everyone on the study is treated with immunotherapy alongside Y90-RadioEmbolization.

Details
Condition Colorectal Cancer Metastatic, Colon Cancer, Metastatic Colorectal Cancer, Rectal Cancer, Liver Metastasis Colon Cancer, Colo-rectal Cancer, Colorectal Adenocarcinoma, Colorectal Neoplasms, Liver Metastases, Colorectal Carcinoma
Treatment durvalumab, yttrium-90 radioembolization
Clinical Study IdentifierNCT04108481
SponsorChandrikha Chandrasekharan
Last Modified on8 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age ≥18 years
Histological or cytological confirmation of colorectal cancer with metastasis to the liver. Mismatch repair or microsatellite instability status of the tumor needs to be known. Tumors need to be mismatch repair proficient (for mismatch repair deficient tumors immunotherapy is already approved)
Patient must have at least 1 liver lesion measurable as defined in the protocol
Must have liver metastases and be appropriate for treatment with Y-90 radioembolization therapy as determined by the treating medical oncologist and interventional radiologist/oncologist, and nuclear medicine physician(s). NOTE: the goal of therapy is safety and parenchymal sparing. Typically, since the treatment is personalized, the goal is to have at least 30% liver parenchymal sparing post treatment
Must have a metastatic focus amendable to biopsy. It is permissible to use same or alternative lesion for biopsy for assessment for tumor response and changes in microenvironment (mandatory pre- and post-Y90-RE biopsy)
At least 2 but no more than 3 lines of therapy allowed in metastatic setting. These include at least treatment with a fluoropyrimidine, oxaliplatin, and/or irinotecan-based therapy, an anti-VEGF therapy and, if RAS wild-type, an anti-EGFR therapy, unless deemed intolerant or not suitable by the treating oncologist. NOTE: adjuvant and/or maintenance chemotherapy does not count as an additional line of therapy. (Patients with more than 3 lines of therapy are at risk for liver disease from prior systemic therapies and would not be reasonable candidates for Y90-RE)
ECOG Performance Status (PS) 0 or 1
Negative serum pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only
Females of childbearing potential (FOCBP), must use appropriate method(s) of contraception. FOCBP are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Additionally, FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with durvalumab plus 5 half-lives of durvalumab (13 weeks) plus 30 days (duration of ovulatory cycle) for a total of 17 weeks post-treatment completion (details in appendix)
Men who are sexually active with FOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with durvalumab plus 5 half-lives of durvalumab plus 90 days (duration of sperm turnover) for a total of 25 weeks post-treatment completion (details in appendix)
Provide written informed consent
Ability to complete questionnaire(s) by themselves or with assistance
Willingness to provide mandatory blood specimens for correlative research (detailed in protocol)
Willingness to provide mandatory tissue specimens for correlative research (detailed in protocol). NOTE: If tissue is deemed inaccessible, patient cannot participate in study
Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
Must have a life expectancy of at least 6 months

Exclusion Criteria

Any of the following laboratory abnormalities
Hemoglobin <8.0 g/dL
Absolute neutrophil count (ANC) <1500/mm3
Platelet count <100,000/mm3
Total bilirubin >1.5 x ULN (except in subjects with Gilbert Syndrome, who cannot have a total bilirubin > 3.0 mg/dL)
Alanine aminotransferase (ALT) and Aspartate transaminase (AST) >2.5 x ULN
Serum creatinine > 1.5 x ULN OR
Calculated creatinine clearance <30 ml/min using the Cockcroft-Gault formula
Any of the following because this study involves an agent that has known genotoxic
Pregnant persons
mutagenic and teratogenic effects
Nursing persons
Persons of childbearing potential who are unwilling to employ adequate contraception
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
Uncontrolled intercurrent illness including, but not limited to, autoimmune disease, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. EXCEPTION: Patients who have adequately controlled autoimmune disease with or without medications are permitted as long as deemed reasonable by treating physician
of the investigator, would make the patient inappropriate for entry into this
study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens
History of unstable cardiac disease defined as one of the following
Untreated central nervous system (CNS) metastatic disease (including spinal cord and leptomeningeal disease). NOTE: Patients with previously treated CNS metastases that are radiographically and neurologically stable for ≥ 6 weeks are permitted
Congestive heart failure > class II New York Heart Association (NYHA). (Appendix II)
Received any other investigational agent incorporating chemotherapy and/or biologics within 14 days prior to first dose of durvalumab which would be considered as a treatment for the primary neoplasm. For patients on active treatment, last treatment and 1st dose of Durvalumab should be at least ≥ 14 days. EXCEPTION: Other forms of concurrent observational studies are permitted
Other active malignancy ≤3 years prior to registration. EXCEPTIONS: Non-melanoma skin cancer, lentigo maligna- in-situ, or carcinoma-in-situ of the cervix. Also prior malignancy already treated with curative intent and with no known active disease present would be considered eligible
Uncontrolled cardiac ventricular arrhythmias. EXCEPTION: Subjects that are stable on anti-arrhythmic therapy are eligible
Unstable angina (angina symptoms at rest) or new onset angina (began ≤ 3 months prior to registration)
Myocardial infarction ≤ 3 months
Patients with renal failure currently requiring dialysis of any kind
Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment within
Active HIV, Hepatitis B or C with uncontrolled disease. EXCEPTION: Patient with non-active, controlled disease will be allowed to participate in study. NOTE: A detailed assessment of HIV and Hepatitis B/C medical history must be done at screening for all patients. HIV 1/2 antibodies, HBsAg and HCV Ab Screen w/Reflex testing are required at screening for all patients
days of first dose of durvalumab. NOTE: Subjects can be screened during
Patients weighing <30kg will be excluded from enrollment
washout period
History of allogenic organ transplantation
History of severe allergic reactions (i.e. Grade 4 allergy, anaphylactic reaction from which the subject did not recover ≤ 6 hours of initiation of supportive care)
Failure to recover from toxicities from prior anti-cancer therapy, defined as having not resolved to National Cancer Institute (NCI) CTCAE version 5.0 Grade ≤ 1. EXCEPTIONS: Alopecia and laboratory values listed per the exclusion criteria. Also subjects with irreversible toxicity that is not reasonably expected to be exacerbated by any investigational products (i.e. hearing loss) will be permitted
Use of steroids. EXCEPTIONS: Systemic glucocorticoids will be permitted as long as it is ≤20 mg of prednisone equivalent. Topical steroids, such as bronchodilators and local steroid injections are also permitted if clinically required
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