RECRUITING

Regorafenib in Combination with Pembrolizumab or Pembrolizumab for MSI-H Colorectal Cancer

Conditions

MSI-H Colorectal Cancer multi-kinase inhibitor receptor tyrosine kinases anti-PD1 blockade immune checkpoint inhibitor vascular endothelial growth factor receptor (VEGFR)

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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

This is a trial of Regorafenib in combination with pembrolizumab for patients with MSI-H colorectal cancer consisting of lead-in phase examining preliminary efficacy and safety, followed by a randomized phase to further examine efficacy.

Official Title

Randomized Trial of Regorafenib in Combination with Pembrolizumab or Pembrolizumab Monotherapy with an Efficacy Lead-in of Regorafenib and Pembrolizumab for Patients with MSI-H Colorectal Cancer

Quick Facts

Study Start:2024-06-26

Study Completion:2029-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06006923

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

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Histologically confirmed mismatch repair deficient or microsatellite instability high advanced stage colorectal cancer 2. Measurable disease (per RECIST v1.1) 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 4. Age \> 18 5. The patient must be able to swallow oral medication. 6. Adequate organ function based on the following lab assessments: 1. ANC must be ≥ 1500/mm3 2. platelet count must be ≥ 100,000/mm3 3. WBC count ≥ 2.5 × 109 /L 4. Hemoglobin must be ≥ 9 g/dL 5. Alkaline phosphatase ≤ 2.5× upper limit of normal (ULN) with the exception of patients with documented liver or bone metastases who should have ALP ≤ 5.0× ULN 6. AST and ALT ≤ 2.5× ULN with the exception of patients with documented liver metastases who may have AST and/or ALT ≤ 5.0× ULN 7. International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation 8. Total bilirubin ≤ 1.5× ULN (≤ 3× ULN if Gilbert syndrome present) 9. Serum albumin ≥ 2.8 g/dL or 28 g/L 10. Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula) or creatinine ≤ 1.5× ULN 7. No more than three cycles of prior fluoropyrimidine-based chemotherapy including folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and, folinic acid, fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI) excluding adjuvant treatment 8. Patients (male or female) of reproductive potential must agree to use an effective method of contraception (as discussed with treating physician) from the time consent is signed, during study therapy, and for at least 8 weeks after the last dose of study therapy. 9. Patients who received no more than 1 cycle of pembrolizumab monotherapy will be still eligible to be enrolled in lead in phase of the trial	1. Prior anti-programmed death 1 (anti-PD-1) or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) based therapy 2. More than 3 cycles of chemotherapy or progression of disease on first line therapy excluding adjuvant treatment and any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment 3. Active autoimmune disease 4. Pregnant or lactating females 5. Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV); patients with undetectable viral load and CD4 count \> 200 will be eligible for enrollment 6. Active untreated brain metastasis 7. Uncontrolled hypertension (HTN: systolic pressure \> 150 mmHg or diastolic pressure \> 90 mmHg on repeated measurements) and cardiovascular events within 12 months of start of treatment 8. Active infection or chronic infection requiring chronic suppressive antibiotics 9. No active cancer such as colon cancer other than adenocarcinoma (e.g., sarcoma, lymphoma, carcinoid) within 1 year 10. Patients with severe hepatic impairment (Child-Pugh C) are excluded as regorafenib has not been studied in this population and exposure might be increased in these patients 11. Major surgical procedure or significant traumatic injury within 28 days before start of study medication 12. Non-healing wound, non-healing ulcer, or non-healing bone fracture 13. Patients with evidence or history of any bleeding diathesis, irrespective of severity 14. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication: 1. Major surgical procedure or significant traumatic injury within 28 days before start of study medication 2. Non-healing wound, non-healing ulcer, or non-healing bone fracture 3. Patients with evidence or history of any bleeding diathesis, irrespective of severity 4. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication

Inclusion Criteria

Exclusion Criteria

1. Histologically confirmed mismatch repair deficient or microsatellite instability high advanced stage colorectal cancer
2. Measurable disease (per RECIST v1.1)
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
4. Age \> 18
5. The patient must be able to swallow oral medication.
6. Adequate organ function based on the following lab assessments:
1. ANC must be ≥ 1500/mm3
2. platelet count must be ≥ 100,000/mm3
3. WBC count ≥ 2.5 × 109 /L
4. Hemoglobin must be ≥ 9 g/dL
5. Alkaline phosphatase ≤ 2.5× upper limit of normal (ULN) with the exception of patients with documented liver or bone metastases who should have ALP ≤ 5.0× ULN
6. AST and ALT ≤ 2.5× ULN with the exception of patients with documented liver metastases who may have AST and/or ALT ≤ 5.0× ULN
7. International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation
8. Total bilirubin ≤ 1.5× ULN (≤ 3× ULN if Gilbert syndrome present)
9. Serum albumin ≥ 2.8 g/dL or 28 g/L
10. Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula) or creatinine ≤ 1.5× ULN
7. No more than three cycles of prior fluoropyrimidine-based chemotherapy including folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and, folinic acid, fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI) excluding adjuvant treatment
8. Patients (male or female) of reproductive potential must agree to use an effective method of contraception (as discussed with treating physician) from the time consent is signed, during study therapy, and for at least 8 weeks after the last dose of study therapy.
9. Patients who received no more than 1 cycle of pembrolizumab monotherapy will be still eligible to be enrolled in lead in phase of the trial

1. Prior anti-programmed death 1 (anti-PD-1) or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) based therapy
2. More than 3 cycles of chemotherapy or progression of disease on first line therapy excluding adjuvant treatment and any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment
3. Active autoimmune disease
4. Pregnant or lactating females
5. Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV); patients with undetectable viral load and CD4 count \> 200 will be eligible for enrollment
6. Active untreated brain metastasis
7. Uncontrolled hypertension (HTN: systolic pressure \> 150 mmHg or diastolic pressure \> 90 mmHg on repeated measurements) and cardiovascular events within 12 months of start of treatment
8. Active infection or chronic infection requiring chronic suppressive antibiotics
9. No active cancer such as colon cancer other than adenocarcinoma (e.g., sarcoma, lymphoma, carcinoid) within 1 year
10. Patients with severe hepatic impairment (Child-Pugh C) are excluded as regorafenib has not been studied in this population and exposure might be increased in these patients
11. Major surgical procedure or significant traumatic injury within 28 days before start of study medication
12. Non-healing wound, non-healing ulcer, or non-healing bone fracture
13. Patients with evidence or history of any bleeding diathesis, irrespective of severity
14. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication:
1. Major surgical procedure or significant traumatic injury within 28 days before start of study medication
2. Non-healing wound, non-healing ulcer, or non-healing bone fracture
3. Patients with evidence or history of any bleeding diathesis, irrespective of severity
4. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication

Contacts and Locations

Study Contact

Clare Grzejka, RN, BSN

CONTACT

412-623-4891

grzejkac@upmc.edu

Debra Diecks, RN, BSN

CONTACT

412-623-8364

diecksda@upmc.edu

Principal Investigator

Ibrahim H Sahin, MD

PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Study Locations (Sites)

AdventHealth Orlando

Orlando, Florida, 32804

United States

Northwestern University

Evanston, Illinois, 60208

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Ibrahim Halil Sahin

Ibrahim H Sahin, MD, PRINCIPAL_INVESTIGATOR, UPMC Hillman Cancer Center

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 Date2024-06-26

Study Completion Date2029-06

Study Record Updates

Study Start Date2024-06-26

Study Completion Date2029-06

Terms related to this study

Keywords Provided by Researchers

multi-kinase inhibitor
receptor tyrosine kinases
anti-PD1 blockade
immune checkpoint inhibitor
vascular endothelial growth factor receptor (VEGFR)

Additional Relevant MeSH Terms

MSI-H Colorectal Cancer