RECRUITING

A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for Rectal Cancer.

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Enrolled patients will receive upfront (week 1) short-course radiotherapy to gross pelvic disease (25Gy in 5fx) in combination with AB928 (150 mg orally, once daily as part of a continuous dose regimen). This will be followed by consolidation chemotherapy (weeks 3-20) with mFOLFOX x9 cycles in combination with AB928 and AB122.

Official Title

A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for Rectal Cancer.

Quick Facts

Study Start:2022-03-31

Study Completion:2030-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05024097

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 90 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically confirmed diagnosis of adenocarcinoma of the rectum * Age ≥ 18 years * ECOG performance status 0-1 * cT3N0 or cT1-3N1 * 5cm from the anal verge * Rectal cancer amenable to total mesorectal excision * No evidence of distant metastases * No prior pelvic radiation therapy * No prior chemotherapy or surgery for rectal cancer * No infections requiring systemic antibiotic treatment * Hgb \>8.0 gm/dL, PLT \> 150,000/mm3, total bilirubin ≤ 1.5x upper limit of normal, AST ≤ upper limit of normal, ALT ≤ 3x upper limit of normal * Female participants or reproductive potential, defined as not surgically sterilized and between menarche and 1 year post menopause, must have a negative serum pregnancy test within 4 weeks prior to initiation of study treatment * Female participants of reproductive potential and male participants with female partners of reproductive potential must remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive measures from the start of study treatment until 30 days after the last dose of etrumadenant, 90 days after the last dose of zimberelimab, whichever is longer * Women with childbearing potential who are negative for pregnancy (urine or blood) and who agree to use effective contraceptive methods. A woman of childbearing potential is defined by one who is biologically capable of becoming pregnant. Reliable contraception should be used from trial screening and must be continued throughout the study. * Male subjects must also agree to use effective contraception.	* Recurrent rectal cancer * Primary unresectable rectal cancer is defined as a primary rectal tumor which, on the basis of either physical exam or pelvic MRI, is demed to be adherent or fixed to adjacent pelvic structures (en bloc resection wll not be achieved with negative margins). * ≥4 regional lymph nodes each ≥10 mm on pelvic MRI * Suspected T4 tumor * Involved radial margin * Serum creatinine level \>1.5x the upper limit of normal * Patients who have received prior pelvic radiotherapy * QTc ≥480 msec using Fredericia's QT correction formula * Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had: * Treatment with known BCRP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of and throughout study treatment * Treatment with known P-gp substrates with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment * Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) and strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment * Any gastrointestinal condition that would preclude the use of oral medications (e.g., difficulty swallowing, nausea, vomiting, or malabsorption) * Prior treatment with an agent targeting the adenosine pathway * History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins * Patients with a history of any arterial thrombitic event within the past 6 months, - Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment would make them inappropriate candidates for entry into this study * Patients with a history of prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer. * Patients with a history of thrombotic episodes, such as deep venous thrombosis, pulmonary embolus, MI or CVA occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Patients who are anticoagulated for atrial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy. * Patients receiving other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibodiy therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody, or other experimental drugs) of any kind are permitted while the patient is receiving study treatment. * Women who are pregnant or breastfeeding. Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to four weeks after the study.

Inclusion Criteria

Exclusion Criteria

* Histologically confirmed diagnosis of adenocarcinoma of the rectum
* Age ≥ 18 years
* ECOG performance status 0-1
* cT3N0 or cT1-3N1
* 5cm from the anal verge
* Rectal cancer amenable to total mesorectal excision
* No evidence of distant metastases
* No prior pelvic radiation therapy
* No prior chemotherapy or surgery for rectal cancer
* No infections requiring systemic antibiotic treatment
* Hgb \>8.0 gm/dL, PLT \> 150,000/mm3, total bilirubin ≤ 1.5x upper limit of normal, AST ≤ upper limit of normal, ALT ≤ 3x upper limit of normal
* Female participants or reproductive potential, defined as not surgically sterilized and between menarche and 1 year post menopause, must have a negative serum pregnancy test within 4 weeks prior to initiation of study treatment
* Female participants of reproductive potential and male participants with female partners of reproductive potential must remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive measures from the start of study treatment until 30 days after the last dose of etrumadenant, 90 days after the last dose of zimberelimab, whichever is longer
* Women with childbearing potential who are negative for pregnancy (urine or blood) and who agree to use effective contraceptive methods. A woman of childbearing potential is defined by one who is biologically capable of becoming pregnant. Reliable contraception should be used from trial screening and must be continued throughout the study.
* Male subjects must also agree to use effective contraception.

* Recurrent rectal cancer
* Primary unresectable rectal cancer is defined as a primary rectal tumor which, on the basis of either physical exam or pelvic MRI, is demed to be adherent or fixed to adjacent pelvic structures (en bloc resection wll not be achieved with negative margins).
* ≥4 regional lymph nodes each ≥10 mm on pelvic MRI
* Suspected T4 tumor
* Involved radial margin
* Serum creatinine level \>1.5x the upper limit of normal
* Patients who have received prior pelvic radiotherapy
* QTc ≥480 msec using Fredericia's QT correction formula
* Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:
* Treatment with known BCRP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of and throughout study treatment
* Treatment with known P-gp substrates with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment
* Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) and strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment
* Any gastrointestinal condition that would preclude the use of oral medications (e.g., difficulty swallowing, nausea, vomiting, or malabsorption)
* Prior treatment with an agent targeting the adenosine pathway
* History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
* Patients with a history of any arterial thrombitic event within the past 6 months, - Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment would make them inappropriate candidates for entry into this study
* Patients with a history of prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
* Patients with a history of thrombotic episodes, such as deep venous thrombosis, pulmonary embolus, MI or CVA occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Patients who are anticoagulated for atrial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy.
* Patients receiving other anticancer or experimental therapy. No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibodiy therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody, or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.
* Women who are pregnant or breastfeeding. Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to four weeks after the study.

Contacts and Locations

Study Contact

Fabiana Gregucci, M.D.

CONTACT

646- 962-3110

fgr4002@med.cornell.edu

Dakota Trick, M.S.

CONTACT

646-962-2196

dat4015@med.cornell.edu

Principal Investigator

Encouse Golden, M.D., Ph.D.

PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Study Locations (Sites)

Weill Cornell Medical College

New York, New York, 10065

United States

Brooklyn Methodist Hospital - NewYork Presbyterian

New York, New York, 11215

United States

New York Presbyterian Hospital - Queens

New York, New York, 11355

United States

Collaborators and Investigators

Sponsor: Weill Medical College of Cornell University

Encouse Golden, M.D., Ph.D., PRINCIPAL_INVESTIGATOR, Weill Medical College of Cornell University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-03-31

Study Completion Date2030-12

Study Record Updates

Study Start Date2022-03-31

Study Completion Date2030-12

Terms related to this study

Additional Relevant MeSH Terms

Rectal Cancer