Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Anti-Infective Agents

Pembrolizumab

Pyrazole

Celecoxib

Interferons

Interferon-alpha

Interferon alpha-2

poly(I).poly(c12,U)

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antiviral Agents

Immunologic Factors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Patients receive rintatolimod IV, celecoxib PO, interferon alpha-2b IV on days 0, 1, and 2 of week 1 and days 7, 8, and 9 of week 2 on study. Patients receive pembrolizumab IV on day 9 and then every 3 weeks after that for up to 4 doses on study. Patients also undergo CT scan or MRI at screening and follow-up and undergo blood sample collection during screening and on study.

Patients receive rintatolimod IV, celecoxib PO, and interferon alpha-2b IV on days 0, 1, and 2 of week 1 and days 7, 8, and 9 of week 2 on study. Patients receive pembrolizumab IV on day 2 of week 1 and then every 3 weeks beginning in week 4 on study. Patients also undergo CT scan or MRI at screening and follow-up, undergo blood sample collection during screening and on study, and may undergo tumor biopsy at screening and follow-up.

Biopsy

Biospecimen Collection

Computed Tomography

Interferon Alpha-2

Magnetic Resonance Imaging

Rintatolimod

Shipra Gandhi

This phase I/IIa trial tests the safety, side effects, and best dose of chemokine modulation therapy (CKM) (rintatolimod, celecoxib, and interferon alpha 2b) in combination with pembrolizumab for the treatment of patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable). CKM drugs such as rintatolimod and interferon alpha 2b work to modify the immune response and tumor-related processes, including tumor cell growth, blood vessel growth, and metastasis. Celecoxib is an anti-inflammatory drug that can cause cell death and may reduce the growth of blood vessels tumors need to grow and spread. Immunotherapy such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CKM therapy prior to pembrolizumab may direct the immune cells to the cancer cells and maximize the effectiveness of pembrolizumab in patients with metastatic or unresectable triple negative breast cancer.

PRIMARY OBJECTIVE:

I. To evaluate the safety profile of modified CKM (celecoxib, rintatolimod and interferon alpha-2b) regimen (replacement of INTRON \[registered trademark\] A, using alternative source of interferon alpha-2b \[IFNalpha2b\]) combined with pembrolizumab therapy in metastatic triple negative breast cancer patients.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of the CKM in combination with pembrolizumab in patients with metastatic triple negative breast cancer (mTNBC) as compared to historic outcomes of pembrolizumab and other anti-PD1/PD-L1 therapies alone, as determined by secondary measures of efficacy including:

Ia. Progression-free survival (PFS); Ib. Overall survival (OS); Ic. Overall response rate (ORR) to the combination therapy using Immune Modulated Response Evaluation Criteria in Solid Tumors (iRECIST); Id. Disease control rate (DCR) using iRECIST.

EXPLORATORY OBJECTIVES:

I. Examine the immune analysis profile of CKM and pembrolizumab combination:

Ia. Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and genetic markers, and their associated PD-1, CD45RA or CD45RO levels; Ib. Correlate PD-L1 expression within both neoplastic and nonneoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and adverse events (AEs); Ic. Correlate immune panel results with ORR, PFS, OS and AEs.

II. Comparison of response assessment criteria for a prospective analysis:

IIa. Response evaluation criteria in solid tumors (RECIST) 1.1 response assessment; IIb. iRECIST response assessment.

OUTLINE: This is a phase I dose escalation study of interferon alpha-2b followed by a phase II study. Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients receive rintatolimod intravenously (IV), celecoxib orally (PO), interferon alpha-2b IV on days 0, 1, and 2 of week 1 and days 7, 8, and 9 of week 2 on study. Patients receive pembrolizumab IV on day 9 and then every 3 weeks after that for up to 4 doses on study. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) at screening and follow-up and undergo blood sample collection during screening and on study.

COHORT II: Patients receive rintatolimod IV, celecoxib PO, and interferon alpha-2b IV on days 0, 1, and 2 of week 1 and days 7, 8, and 9 of week 2 on study. Patients receive pembrolizumab IV on day 2 of week 1 and then every 3 weeks beginning in week 4 on study. Patients also undergo CT scan or MRI at screening and follow-up, undergo blood sample collection during screening and on study, and may undergo tumor biopsy at screening and follow-up.

Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer

Phase I/IIa Clinical Trial Evaluating the Safety and Efficacy of Rintatolimod Combined With IFNα2b (Bioferon®) to Enhance the Effectiveness of Pembrolizumab in Patients With Metastatic Triple Negative Breast Cancer

The dose limiting toxicities will be summarized by cohort using frequencies and relative frequencies.

Will be summarized using standard Kaplan-Meier methods, with estimates of the median survival obtained with 90% confidence intervals.

Evaluated using Immune Modulated Response Evaluation Criteria in Solid Tumors. Will be summarized using frequencies and relative frequencies, and obtained with 90% confidence intervals.

Will be summarized using frequencies and relative frequencies and obtained with 90% confidence intervals.

National Cancer Institute (NCI)

Roswell Park Cancer Institute

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Adenocarcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antipyretics

Fibrinolytic Agents

Platelet Aggregation Inhibitors

Aspirin

Patients receive aspirin PO BID on days -7 to 7. Patients also receive recombinant interferon alfa-2b IV over 20 minutes and rintatolimod IV over 2 hours on days 1-3 and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24..

Patients receive aspirin PO BID on days -7 to 7 and rintatolimod IV over 2 hours on days 1-3,and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24.

Patients undergo radical prostatectomy about 4 weeks after enrollment.

Radical Prostatectomy

Recombinant Interferon Alfa-2b

Gurkamal S Chatta

This phase II trial studies how well aspirin and rintatolimod with or without interferon-alpha 2b work in treating patients with prostate cancer before surgery. Aspirin may help to keep the prostate cancer from coming back. Rintatolimod may stimulate the immune system and interfere with the ability of tumor cells to grow and spread. Interferon-alpha 2b may improve the body's natural response to infections and may slow tumor growth. It is not yet known how well rintatolimod, aspirin, and interferon-alpha 2b work in treating patients with prostate cancer undergoing surgery.

PRIMARY OBJECTIVES:

I. Assess the immunomodulatory effectiveness of the combination of rintatolimod and aspirin with or without recombinant interferon alfa-2b (interferon \[IFN\]-alpha), in participants with localized prostate cancer undergoing radical prostatectomy.

SECONDARY OBJECTIVES:

I. Assess the safety and toxicity of the treatment combinations in participants with localized prostate cancer undergoing radical prostatectomy.

II. Assess the antitumor activity between treatment arms.

EXPLORATORY OBJECTIVES:

I. Compare the resected tumor tissue specimen and surrounding tissue samples of both study arms (pre versus \[vs\] post-chemokine modulatory \[CKM\] treatment, with vs without CKM, CKM doublet vs CKM triplet) with regards to infiltrating T cell subtypes, effector T cell (Teff)/regulatory T cell (Treg) ratios, CD11b+ myeloid-derived suppressor cell (MDSC); the expression of chemokine receptors and immune checkpoint molecules on immune cells; local expression of Teff-attracting chemokines and Treg/MDSC-favoring chemokines; ribonucleic acid (RNA) signatures of groups of immune-regulatory genes that are modulated by the CKM regimen.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive aspirin orally (PO) two times a day (BID) from day -7 to 7 days prior to surgery. Patients also receive recombinant interferon alfa-2b intravenously (IV) over 20 minutes and rintatolimod IV over 2 hours on days 1-3, and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24.

ARM II: Patients receive aspirin PO BID from day -7 to 7 days prior to surgery and rintatolimod IV over 2 hours on days 1-3 and 8-10 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on or between day 17-24.

ARM III: Patients undergo radical prostatectomy about 4 weeks after enrollment.

After completion of study treatment, patients are followed up at 30 days.

Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery

Randomized Phase 2 Study: Neoadjuvant Conditioning of Prostate Cancer Tumor Microenvironment Using a Novel Chemokine-Modulating Regimen

This will be assessed by the increase in the total number of tumor infiltrating CD8+ T cells in the radical prostatectomy specimen (measured as cell density of CD8+ cell by immunohistochemistry), comparing Arm A versus Arm B versus Arm C. Will be natural log transformed prior to analysis. The primary analysis will consist of testing the single degree of freedom planned contrast at alpha = .10 that the 3 treatment means are in the ratio of 3:2:1 (contrast coefficients 3, -2, -1) for groups A, B and C, respectively groups. If this test rejects the null hypothesis of no group differences, will proceed to estimate group means and pairwise differences between groups with 90% confidence intervals. Non-overlapping confidence intervals will serve as evidence of differential treatment effects.

Spearman rank correlation coefficients will be used to estimate the correlation between CD8+ tumor infiltrate, pathologic response rate and prostate specific antigen (PSA) response.

Spearman rank correlation coefficients will be used to estimate the correlation between CD8+ tumor infiltrate, pathologic response rate and PSA response.

Will be evaluated with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

AIM ImmunoTech Inc.

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Pancreatic Cancer

Folfirinox

Subjects will receive rintatolimod \[intravenous (IV)\], up to 400 mg twice weekly until disease progression.

Subjects will be followed / no treatment until evidence of disease progression.

Diane Young

Kher Lee Ng, PhD

Jessica E Delaney, BSN

Kelsey Klute, MD

Carrie Smith

Nashat Y. Gabail, MD

Colette Treperinas

Vincent Picozzi, MD

David R Strayer, MD

The purpose of this study is to assess the safety and efficacy of Ampligen in patients with locally advanced pancreatic adenocarcinoma

This is a Phase 2, randomized, open-label controlled study to evaluate the efficacy and safety of Ampligen treatment compared to a control group / no treatment following FOLFIRINOX treatment in subjects with locally advanced pancreatic adenocarcinoma.

Ampligen Compared to No Treatment Following FOLFIRINOX in Subjects With Locally Advanced Pancreatic Adenocarcinoma

A Phase 2, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Ampligen® Compared to Control Group / No Treatment Following FOLFIRINOX in Subjects With Locally Advanced Pancreatic Adenocarcinoma

PFS is defined as the time, in months, from date of randomization to date of the first documentation of definitive disease progression as per RECIST v1.1 (the initial progressive disease (PD)) or death due to any cause.

OS is defined as patients who are alive at time of analysis

OS is defined as the time from date of Visit 2/First Treatment to death due to any cause.

ORR is defined as the proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) as assessed by RECIST v1.1

DoR is defined as the time from the date of the first documentation of objective tumor response (CR or PR) to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

Amarex Clinical Research

Symptoms and General Pathology

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Disease Attributes

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Pharmaceutical Solutions

Cisplatin

Immunomodulating Agents

Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution.

200 mg by IP administration over 1-2 hours

200 mg will be administered as a 30 minute IV infusion

Robert Edwards, MD

Brenda Steele, RN

This is a phase II single arm efficacy/safety trial that will evaluate the effectiveness of combining intensive locoregional intraperitoneal (IP) chemoimmunotherapy of cisplatin with IP rintatolimod (TLR-3 agonist) and IV infusion of the checkpoint inhibitor pembrolizumab (IVP) for patients with recurrent platinum-sensitive ovarian cancer (OC).

Patients will receive a total of six treatment cycles, at 3-week intervals. The study will use an IP neoadjuvant approach (IP chemoimmunotherapy of cisplatin with IP rintatolimod and IV infusion of pembrolizumab), followed by interval cytoreduction (usually laparoscopically) of residual tumor. Cytoreduction will occur approximately 4 weeks after the fourth treatment cycle. Post-surgery the investigators will consolidate with 2 additional courses of same chemo-immunotherapy regimen. Catheter will be removed 12 weeks after the last treatment. All surgical procedures, if done laparoscopically, are outpatient and will yield up to three serial biopsies of the tumor sites: 1) at catheter placement; 2) at interval cytoreduction which consists of removal of any visible tumor sites and the site biopsied initially whether tumor is present or not; 3) at catheter removal, when site of first tumor biopsy will be re-biopsied for pathologic response.

Ovarian cancer is limited to the female population.

Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer

The proportion of subjects with the best response of complete response (CR), or partial response (PR) per Response Evaluation Criteria for Solid Tumors (RECIST 1.1). Per RECIST 1.1 , CR is defined as all target lesions gone; PR is defined as a \> 30% decrease in size of lesion from baseline.

The length of time during and after study treatment that a patient remains alive without worsening disease. Per RECIST 1.1, progression is defined as a \> 20% increase from smallest sum of longest (lesion) diameter recorded since treatment started (best response - target lesions) and/or, enlargement of non-target lesions.

Within-patient changes in number of CD8+ cells present in tumor tissue and peritoneal fluid.

Within-patient changes in number of CD3+ cells present in tumor tissue and peritoneal fluid.

Merck Sharp & Dohme LLC

Robert Edwards

Professor

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Antibodies

Durvalumab

Immunoglobulins

1500mg Durvalumab administered via IV infusion once every first day of a 28 day cycle for a total of maximum 12 cycles (12 infusions in total).

200-400mg Rintatolimod administered via IV infusion twice per week for a total of 6 weeks (12 infusions in total).

TLR-3 agonist, synthetic double-stranded ribonucleic acid (poly I:C12U)

Songul Kucukcelebi, MD

Judith Verhagen, PhD

Marjolein Homs, MD, PhD

Casper van Eijck, Prof, MD, PhD

H Verheul, Prof, MD, PhD

Marjolein Homs, PhD

Pancreatic ductal adenocarcinoma (PDAC) is estimated to become the second leading cause of cancer-related death by 2030. Effective management of PDAC is challenged by a combination of late diagnosis, lack of effective screening methods and high risk of early metastasis. Although systemic chemotherapy improves survival, 5-year survival is only 6%. Chemotherapy efficacy is attenuated by innate and acquired drug resistance of tumor cells, a strong desmoplastic reaction that limits local accessibility of drugs and a "cold" tumor microenvironment (TME) with high infiltrating levels of immunosuppressive cells. In PDAC, increased T cell exhaustion defined by increased PD-1/PD-L1 activity in both peripheral blood and tumor microenvironment, is associated with poor prognosis. Hence the rationale for targeting the PD-1/PD-L1 axis with the aim to release the "brake" and exert an anti-tumor response. In PDAC successful results with Immune Checkpoint Inhibition (ICI) monotherapy are limited and combination therapy with other agents is encouraged; specifically agents that induce dendritic cell priming. We hypothesize that combination therapy of ICI therapy with a toll like receptor 3 (TLR-3) agonist is a potential effective strategy. TLR-3 agonists are hypothesized to increase dendritic cell maturation and cross-priming naïve cytotoxic CD8 T cells while eliminating regulatory T-cell attraction, thereby acting as an immune-boosting agent. We propose that rintatolimod/durvalumab-combination therapy is feasible and may induce synergistic anti-tumor immune responses in PDAC.

Rationale: Pancreatic ductal adenocarcinoma (PDAC) is estimated to become the second leading cause of cancer-related death by 2030. Effective management of PDAC is challenged by a combination of late diagnosis, lack of effective screening methods and high risk of early metastasis. Although systemic chemotherapy improves survival, 5-year survival is only 6%. Chemotherapy efficacy is attenuated by innate and acquired drug resistance of tumor cells, a strong desmoplastic reaction that limits local accessibility of drugs and a "cold" tumor microenvironment (TME) with high infiltrating levels of immunosuppressive cells. In PDAC, increased T cell exhaustion defined by increased PD-1/PD-L1 activity in both peripheral blood and tumor microenvironment, is associated with poor prognosis. Hence the rationale for targeting the PD-1/PD-L1 axis with the aim to release the "brake" and exert an anti-tumor response. In PDAC successful results with Immune Checkpoint Inhibition (ICI) monotherapy are limited and combination therapy with other agents is encouraged; specifically agents that induce dendritic cell priming. We hypothesize that combination therapy of ICI therapy with a toll like receptor 3 (TLR-3) agonist is a potential effective strategy. TLR-3 agonists are hypothesized to increase dendritic cell maturation and cross-priming naïve cytotoxic CD8 T cells while eliminating regulatory T-cell attraction, thereby acting as an immune-boosting agent. We propose that rintatolimod/durvalumab-combination therapy is feasible and may induce synergistic anti-tumor immune responses in PDAC.

Objective: The primary objective of the safety run-in (phase Ib) is to determine the safety of combination therapy with durvalumab and rintatolimod. The primary objective of the phase II trial is to determine the clinical benefit rate of combination therapy with durvalumab and rintatolimod. The secondary objective is to explore the immunogenic effect and survival rates after combination therapy.

Study design: Exploratory, open-label, single center, phase I-II study. In phase 1 between 9 and max. 18 patients will be included. In the phase II study between 13 and 25 patients will be included.

Study population: Adult patients with metastatic PDAC who completed standard of care (chemotherapy FOLFIRINOX) and have radiologically confirmed stable disease according to RECIST version 1.1 criteria.

Intervention: All included patients will receive combination therapy with rintatolimod and durvalumab. Patients will start with rintatolimod 200mg via IV infusion twice per week for a total of 6 weeks (12 doses). Rintatolimod dose will be escalated to 400mg according to a 3+3 DLT design. The first dose of rintatolimod will be administered preferably 4-6 weeks after the last chemotherapy FOLFIRINOX dose. After two doses of rintatolimod, the first dose of durvalumab 1500mg via IV infusion will be introduced in week 2. Patients will continue to receive 1500 mg durvalumab via IV infusion every 4 weeks for up to a maximum of 48 weeks (up to 12 doses/cycles) with the last administration on week 48 or until confirmed disease progression according to Response Evaluation Criteria in solid Tumors (RECIST 1.1), unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Main study parameters/endpoints: The primary objective of the safety run-in (phase Ib) is to determine safety of combination therapy with durvalumab and rintatolimod.

The primary objective of the phase II trial is to determine the clinical benefit rate of combination therapy with durvalumab and rintatolimod.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will receive 12 doses of rintatolimod via IV infusion and a max. of 12 doses durvalumab via IV infusion. In addition, they will undergo additional blood sampling in order to determine tumor-specific immune and tumor marker responses.

Intravenous administration of medication and blood sampling can cause bruising or slight short-term discomfort. In previously performed trials, monotherapy with rintatolimod and monotherapy with durvalumab proved to be safe showing a low toxicity profile. Therefore we do not expect any major side-effects of this treatment in our patient population.

However, combination treatment with rintatolimod and durvalumab has not been investigated yet, and a synergistic effect can induce unwanted side effects. To determine the safety of combination therapy, a limited number of patients will be included in the safety run-in to determine the RP2D. In addition, to explore the local anti-tumor effect of combination therapy, biopsies will be performed before start and after 12 weeks of treatment in a subset of the included patients.

Exploratory, non-randomized, open-label, single center, phase I-II study

Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy

The primary endpoint of the safety run-in (phase Ib) is the recommended phase II dose (RP2D) defined by the highest dose per protocol without dose-limiting toxicity (DLT) according to a 3+3 design related to the intervention. A DLT is defined as the occurrence of an adverse event (AE) that is at least possibly related to the investigational product (IP) or investigational regimen (IR), with two exceptions: any grade of vitiligo or alopecia will not qualify as a DLT. The DLT assessment period is from the time of first dose of IP/IR and ends upon administration of the first dose of IP/IR on Cycle 2, Day 1 (28 day cycle). Toxicities will be scored according to CTC criteria version 5.0 (Published November 27th, 2017). All participants that cannot complete the combination therapy as planned due to directly related toxicity will be discussed in the Study Steering Committee and they will determine whether the patient is classified as having a DLT.

Response is defined as stable disease, partial or complete response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), determined 6 months after start of combination therapy. If the number of responses is ≥ 4 out of 25 patients further research of this treatment regime is justified. Furthermore, the lower boundary of the 90% CI should be higher than 5% to justify further research of this treatment regime.

Overall survival (OS) of participants will be defined as the time between start combination therapy with durvalumab and rintatolimod to date of death

Progression free survival (PFS), defined as the time between start of combination therapy with durvalumab and rintatolimod to date of progression (according to RECIST criteria version 1.1) or death, whichever occurs first

During the study period peripheral blood samples will be collected. The immune profile will be explored in treatment naïve blood samples and compared in paired blood samples after combination therapy. Also, immuno-oncology gene expression signatures will be determined using multiplex gene expression analysis. Immunogenic efficacy, defined as \>50% increase in circulating Ki67+ CD 8+ T cell in the peripheral blood, will be evaluated 12 weeks after combination therapy

During the study period tumor site biopsies will be taken from an accessible metastasis site. One before and one after 3 study treatments. The immune profile will be explored in treatment naïve tissue samples and compared in paired tissue samples after combination therapy. Also, immuno-oncology gene expression signatures will be determined using multiplex gene expression analysis.

For all participants quality of life questionnaires will be collected using questionnaires EORTC QLQ-C30

AstraZeneca BV

Joachim Aerts, MD PhD

Prof. dr.

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

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.

Questionnaire Administration

Christos Fountzilas, MD

This phase IIa trial studies how well rintatolimod and pembrolizumab works in treating patients with colorectal cancer that does not respond to treatment (refractory), has spread to other places in the body (metastatic), or otherwise cannot be removed by surgery (unresectable). Rintatolimod is an immuno-oncology agent that can stimulate the immune system. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving rintatolimod and pembrolizumab together may work better than standard of care in treating patients with colorectal cancer.

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.

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

Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and estimated using a 90% confidence interval obtained using Jeffrey?s prior method.

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.

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.

Determined by immune-modified (i)RECIST and estimated using a 90% confidence interval obtained using Jeffrey?s prior method.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rintatolimod, Celecoxib and Interferon Alpha 2b With Pembrolizumab For the Treatment of Patients With Metastatic or Unresectable Triple Negative Breast Cancer	NCT05756166	Anatomic Stage ... Metastatic Trip... Unresectable Tr...	Biopsy Biospecimen Col... Celecoxib Computed Tomogr... Interferon Alph... Magnetic Resona... Pembrolizumab Rintatolimod	18 Years -	Roswell Park Cancer Institute
Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery	NCT03899987	Prostate Adenoc... Stage I Prostat... Stage II Prosta... Stage IIA Prost... Stage IIB Prost... Stage IIC Prost... Stage III Prost... Stage IIIA Pros... Stage IIIB Pros... Stage IIIC Pros...	Aspirin Radical Prostat... Recombinant Int... Rintatolimod	18 Years -	Roswell Park Cancer Institute
Ampligen Compared to No Treatment Following FOLFIRINOX in Subjects With Locally Advanced Pancreatic Adenocarcinoma	NCT05494697	Pancreatic Canc...	Rintatolimod	18 Years -	AIM ImmunoTech Inc.
Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer	NCT03734692	Ovarian Cancer ...	Rintatolimod Pembrolizumab Cisplatin	18 Years -	University of Pittsburgh
Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer	NCT03734692	Ovarian Cancer ...	Rintatolimod Pembrolizumab Cisplatin	18 Years -	University of Pittsburgh
Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy	NCT05927142	Metastatic Panc...	Durvalumab Rintatolimod	18 Years -	Erasmus Medical Center
Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy	NCT05927142	Metastatic Panc...	Durvalumab Rintatolimod	18 Years -	Erasmus Medical Center
Rintatolimod and Pembrolizumab for the Treatment of Refractory Metastatic or Unresectable Colorectal Cancer	NCT04119830	Metastatic Colo... Microsatellite ... Mismatch Repair... Refractory Colo... Stage III Color... Stage IIIA Colo... Stage IIIB Colo... Stage IIIC Colo... Stage IV Colore... Stage IVA Color... Stage IVB Color... Stage IVC Color... Unresectable Co...	Pembrolizumab Questionnaire A... Rintatolimod	18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for rintatolimod

Every month we try and update this database with for rintatolimod cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.