- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04119830
Rintatolimod and Pembrolizumab for the Treatment of Refractory Metastatic or Unresectable Colorectal Cancer
A Phase IIa Study of Rintatolimod Plus Pembrolizumab in Refractory Metastatic Colorectal Cancer
Study Overview
Status
Conditions
- Metastatic Colorectal Adenocarcinoma
- Refractory Colorectal Adenocarcinoma
- Microsatellite Stable
- Stage IV Colorectal Cancer AJCC v8
- Stage IVA Colorectal Cancer AJCC v8
- Stage IVB Colorectal Cancer AJCC v8
- Stage IVC Colorectal Cancer AJCC v8
- Stage III Colorectal Cancer AJCC v8
- Stage IIIA Colorectal Cancer AJCC v8
- Stage IIIB Colorectal Cancer AJCC v8
- Stage IIIC Colorectal Cancer AJCC v8
- Unresectable Colorectal Carcinoma
- Mismatch Repair Proficient
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. Determine the objective response rate of patients with metastatic colorectal cancer (mCRC) treated with rintatolimod + pembrolizumab.
SECONDARY OBJECTIVES:
I. Establish the adverse event profile of combining rintatolimod and pembrolizumab.
II. Estimate the median progression free survival and overall survival of patients with mCRC treated with rintatolimod and pembrolizumab.
III. Determine the immune objective response rate of patients with mCRC treated with rintatolimod + pembrolizumab.
EXPLORATORY OBJECTIVES:
I. Assess modulation of the levels of CD8alpha expression and cytotoxic T-lymphocyte (CTL) density pre- and post-therapy.
II. Assess chemokine levels in the tumor microenvironment and peripheral blood, including effector T cell (Teff)-attracting and regulatory T cell (Treg)-favoring chemokines.
III. Characterize the fecal microbiotic profile and correlate those results with antitumor immune responses.
OUTLINE:
Patients receive rintatolimod intravenously (IV) over 30 minutes on days 1-3 and pembrolizumab IV over 30 minutes on day 3. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 4, patients receive rintatolimod IV over 30 minutes and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months from the first dose in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, and every 6 months for up to 2 years.
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
-
Buffalo, New York, United States, 14263
- Roswell Park Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Biopsy proven colorectal adenocarcinoma which is metastatic or otherwise unresectable
- Microsatellite stable/mismatch-repair proficient (by immunohistochemistry [IHC] and/or polymerase chain reaction [PCR])
Progression following: a fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR targeted therapy (if anti-EGFR therapy is appropriate), bevacizumab (if appropriate)
- NOTE: Patients who could not tolerate standard agents because of unacceptable, but reversible, toxicity necessitating their discontinuation will be allowed to participate
- Amenable to undergoing serial tumor biopsy (x 2). NOTE: patients with inaccessible lesions, where the investigator deems biopsy to be unsafe or where biopsy is otherwise contraindicated, are still eligible to enroll, with review and approval of the principal investigator (PI)
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Absolute neutrophil (ANC) count >= 1500/uL
- Platelets >= 100,000/uL
- Hemoglobin >= 9 g/dL
- Serum or plasma creatinine =< 1.5 X upper limit of normal (ULN) or measured or calculated creatinine clearance by Cockcroft Gault Equation >= 30 ml/min for subjects with creatinine levels > 1.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN or (=< 5 x ULN if the patient has liver metastases)
- Bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN
- International normalized ratio (INR) or prothrombin time (PT): =< 1.5 unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT): =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
- Female participants of childbearing potential are to have a negative serum pregnancy test
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment
- A male participant must agree to use an adequate method of contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
- Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Exclusion Criteria:
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to start of study treatment
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette?Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
- Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study drug
- Has a known additional malignancy that is progressing or in the opinion of the investigator is likely to interfere with properly assessing treatment efficacy. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Have a severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
- Has previously received rintatolimod, poly-ICLC or derivatives
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Woman of childbearing potential who has a positive urine pregnancy test within 72 hours prior to start of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV), unless on highly active antiretroviral therapy (HAART) with undetectable viral load
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection
- Pregnant or nursing female participants
- Unwilling or unable to follow protocol requirements
- Any condition which in the investigator?s opinion deems the participant an unsuitable candidate to receive study drug
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (rintatolimod, pembrolizumab)
Patients receive rintatolimod IV over 30 minutes on days 1-3 and pembrolizumab IV over 30 minutes on day 3. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Beginning in cycle 4, patients receive rintatolimod IV over 30 minutes and pembrolizumab IV over 30 minutes on day 1.
Cycles repeat every 21 days for up to 24 months from the first dose in the absence of disease progression or unacceptable toxicity.
|
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate
Time Frame: At 6 months following completion of enrollment (at 24 months)
|
Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and estimated using a 90% confidence interval obtained using Jeffrey?s prior method.
|
At 6 months following completion of enrollment (at 24 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events
Time Frame: Up to 2 years
|
Toxicities and adverse events (according to Common Terminology Criteria in Adverse Events [CTCAE] version 5.0) will be summarized by attribution and grade using frequencies and relative frequencies.
|
Up to 2 years
|
Median progression free survival
Time Frame: From the time of first dosing of study treatment combination to documented disease progression by RECIST 1.1, assessed up to 2 years
|
Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and 6/12-month survival rates will be obtained with 95% confidence intervals.
|
From the time of first dosing of study treatment combination to documented disease progression by RECIST 1.1, assessed up to 2 years
|
Overall survival
Time Frame: From the time of first dosing of study treatment combination to time of death or initiation of a new therapy, whichever occurs first, assessed up to 2 years
|
Will be summarized using standard Kaplan-Meier methods; where estimates of median survival and 6/12-month survival rates will be obtained with 95% confidence intervals.
|
From the time of first dosing of study treatment combination to time of death or initiation of a new therapy, whichever occurs first, assessed up to 2 years
|
Objective response rate
Time Frame: Up to 2 years
|
Determined by immune-modified (i)RECIST and estimated using a 90% confidence interval obtained using Jeffrey?s prior method.
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Adenocarcinoma
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Pembrolizumab
- poly(I).poly(c12,U)
Other Study ID Numbers
- I 74118 (OTHER: Roswell Park Cancer Institute)
- NCI-2019-06440 (REGISTRY: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Colorectal Adenocarcinoma
-
Zhejiang Cancer HospitalNot yet recruitingMetastatic Colorectal Cancer | Metastatic Colorectal Adenocarcinoma | CRCChina
-
Mayo ClinicCompletedMetastatic Colorectal Adenocarcinoma | Metastatic Colon Adenocarcinoma | Metastatic Colorectal Carcinoma | Metastatic Rectal Adenocarcinoma | Stage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Metastatic... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingMetastatic Colorectal Adenocarcinoma | Metastatic Colon Adenocarcinoma | Metastatic Rectal Adenocarcinoma | Stage IV Colon Cancer AJCC v8 | Stage IV Colorectal Cancer AJCC v8 | Stage IV Rectal Cancer AJCC v8 | Metastatic Microsatellite Stable Colorectal CarcinomaUnited States
-
Georgetown UniversityNational Cancer Institute (NCI); Mayo Clinic; Emory University; Indiana University and other collaboratorsTerminatedMetastatic Colorectal Cancer | Pancreatic Adenocarcinoma | Colorectal Adenocarcinoma | Metastatic Pancreatic CancerUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Not yet recruitingMetastatic Colorectal Adenocarcinoma | Metastatic Colon Adenocarcinoma | Metastatic Rectal Adenocarcinoma | Stage IV Colon Cancer AJCC v8 | Stage IV Colorectal Cancer AJCC v8 | Stage IV Rectal Cancer AJCC v8United States
-
University of Campania "Luigi Vanvitelli"Active, not recruitingMetastatic Colorectal AdenocarcinomaItaly
-
Centre Hospitalier Universitaire DijonCompletedMetastatic Colorectal AdenocarcinomaFrance
-
Memorial Sloan Kettering Cancer CenterBayer; State University of New York - Downstate Medical Center; Queens Cancer...Active, not recruitingMetastatic Colorectal AdenocarcinomaUnited States
-
Hunan Cancer HospitalCompletedMetastatic Colorectal AdenocarcinomaChina
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingMetastatic Colorectal Adenocarcinoma | Stage IV Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Metastatic Microsatellite Stable Colorectal Carcinoma | Advanced Microsatellite Stable Colorectal Carcinoma | Advanced Colorectal AdenocarcinomaUnited States
Clinical Trials on Questionnaire Administration
-
Fondazione Don Carlo Gnocchi OnlusUnknown
-
Centre Oscar LambretCentre Hospitalier Universitaire de BesanconTerminated
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI)TerminatedHealth Status UnknownUnited States
-
Istanbul Aydın UniversityCompleted
-
Hospital Clínico Universitario de ValladolidRed Centinela Sanitaria de Castilla y León (RCSCYL); Centro Nacional de Gripe... and other collaboratorsRecruitingMigraine | Headache Disorders | Viral Infection | Influenza -Like Illness | Head PainSpain
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingBreast Ductal Carcinoma In Situ | Invasive Breast Carcinoma | COVID-19 Infection | Hereditary Breast CarcinomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Recurrent Lymphoma | Recurrent Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Recurrent Plasma Cell Myeloma | Caregiver | Recurrent LeukemiaUnited States
-
I.M. Sechenov First Moscow State Medical UniversityAgency of Social Information St. PetersburgActive, not recruiting
-
I.M. Sechenov First Moscow State Medical UniversityActive, not recruitingShoulder ArthropathyRussian Federation
-
Karolinska University HospitalSahlgrenska University Hospital, Sweden; University Hospital, Linkoeping; Skane...Active, not recruitingQuality of Life | Vulvar CancerSweden