RECRUITING

Safety of SBRT With Anti-PD1 and Anti-IL-8 for the Treatment of Multiple Metastases in Advanced Solid Tumors and Melanoma

Conditions

Melanoma Unresectable Solid Tumors Neoplasms Neoplasms by Histologic Type Neoplasms by Site Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Nivolumab Anti-PD-1 monoclonal antibody (mAb)Anti-IL-8 Stereotactic Body Radiotherapy (SBRT)

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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

Nivolumab (and other agents affecting the anti-programmed death-1 \[anti-PD-1\] pathway) have demonstrated anti-tumor activity in multiple tumor types. Combinations of immune-oncology (IO) agents with complimentary mechanisms as well as radiation represent a promising strategy to improve response rates to immunotherapy and overcome resistance. In this phase I/Ib study, radiation will be used in combination with IO agents nivolumab and anti-IL-8 (BMS-986253) to assess toxicity by organ system and then assess the preliminary efficacy of the treatment regimen. In Part 1, the study will determine the safe doses of radiation by organ site in conjunction with nivolumab and BMS-986253. In Part 2, the treatment regimen will be investigated in melanoma, prioritizing acral melanoma, to describe the response rate to treatment as well as other clinical and safety outcomes. The study will also provide the opportunity to evaluate changes in the tumor microenvironment induced by the treatment.

Official Title

Phase I Study Investigating the Safety of Stereotactic Body Radiotherapy (SBRT) With Anti-PD1 and Anti-IL-8 for the Treatment of Multiple Metastases in Advanced Solid Tumors and Melanoma

Quick Facts

Study Start:2021-11-29

Study Completion:2027-05-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04572451

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
* SAFETY COHORT 1. Patients with advanced/metastatic/unresectable solid tumors progressed on standard therapies. Patients with melanoma and RCC will make up approximately 30% of total cohort. 2. Patients with 1-4 tumor sites that can be irradiated safely 3. Age \> or equal 18 years 4. ECOG performance status 0 or 1 5. Patients must have normal organ and marrow function as defined below: * Leukocytes ≥ 3000/mcL; * absolute neutrophil count ≥ 1500/mcL; * Platelets ≥ 100,000/mcL; * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) ; * Total bilirubin ≤ 1.5 × ULN (except participants with Gilbert's Syndrome who must have normal direct bilirubin) * Serum creatinine ≤ 1.5 × ULN Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam 6. Ability to understand and the willingness to sign a written informed consent document. 7. Reproductive status * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study treatment. * Women must not be breastfeeding. * WOCBP must agree to follow instructions for method(s) of contraception (Appendix 5) for the duration of study treatment plus 5 half-lives of nivolumab plus 30 days (duration of ovulatory cycle), for a total of 155 days post treatment completion. Local laws and regulations may require use of alternative and/or additional contraception methods. * WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, but should still undergo pregnancy testing as described in this section. * Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (Appendix4) during combination treatment with study treatment BMS-986253 and nivolumab, plus 5 half-lives of nivolumab (∼125 days), plus 90 days (duration of sperm turnover), for a total of 215 days post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. * EFFICACY COHORT 1. Patients with anti-PD1/PDL1 refractory melanoma 2. Patients with 1-4 tumor sites that can be irradiated safely 3. Age ≥ 18 years 4. ECOG performance status 0 or 1 5. Patients must have normal organ and marrow function as defined above for safety cohort 6. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam 7. Ability to understand and the willingness to sign a written informed consent document.	1. Known or suspected CNS metastases, with the following exceptions: 2. Medical History and Concurrent Diseases * Patients who are receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and BMS-986253 * Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: * A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent * Subjects with history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, hormone replacement after endocrinopathy). * Subject has been administered prior chemotherapy or immunotherapy at any time, and any with radiation therapy within 4 weeks prior to time of consent or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to previously administered agent. 1. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. 2. Subjects with endocrinopathy which is adequately controlled with hormone replacement therapy are an exception to this criterion and may qualify for the study. * If subject underwent major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. * Subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * A known or underlying medical condition that, in the opinion of the investigator could make the administration of study drug hazardous to the subject or could adversely affect the ability of the subject to comply with or tolerate study therapy. * Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with the study drugs. * Subjects who are unable to undergo venipuncture and/or tolerate venous access * Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days prior to initiation of study drug therapy * Subjects who are on immunosuppressive therapy (systemic steroids 10mg and more daily use) * Prisoners or subjects who are involuntarily incarcerated * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness * Inability to comply with restrictions and prohibited activities and treatments

Inclusion Criteria

Exclusion Criteria

* SAFETY COHORT
1. Patients with advanced/metastatic/unresectable solid tumors progressed on standard therapies. Patients with melanoma and RCC will make up approximately 30% of total cohort.
2. Patients with 1-4 tumor sites that can be irradiated safely
3. Age \> or equal 18 years
4. ECOG performance status 0 or 1
5. Patients must have normal organ and marrow function as defined below:
* Leukocytes ≥ 3000/mcL;
* absolute neutrophil count ≥ 1500/mcL;
* Platelets ≥ 100,000/mcL;
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) ;
* Total bilirubin ≤ 1.5 × ULN (except participants with Gilbert's Syndrome who must have normal direct bilirubin)
* Serum creatinine ≤ 1.5 × ULN Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam
6. Ability to understand and the willingness to sign a written informed consent document.
7. Reproductive status
* Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study treatment.
* Women must not be breastfeeding.
* WOCBP must agree to follow instructions for method(s) of contraception (Appendix 5) for the duration of study treatment plus 5 half-lives of nivolumab plus 30 days (duration of ovulatory cycle), for a total of 155 days post treatment completion. Local laws and regulations may require use of alternative and/or additional contraception methods.
* WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, but should still undergo pregnancy testing as described in this section.
* Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (Appendix4) during combination treatment with study treatment BMS-986253 and nivolumab, plus 5 half-lives of nivolumab (∼125 days), plus 90 days (duration of sperm turnover), for a total of 215 days post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.
* EFFICACY COHORT
1. Patients with anti-PD1/PDL1 refractory melanoma
2. Patients with 1-4 tumor sites that can be irradiated safely
3. Age ≥ 18 years
4. ECOG performance status 0 or 1
5. Patients must have normal organ and marrow function as defined above for safety cohort
6. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam
7. Ability to understand and the willingness to sign a written informed consent document.

1. Known or suspected CNS metastases, with the following exceptions:
2. Medical History and Concurrent Diseases
* Patients who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and BMS-986253
* Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
* A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
* Subjects with history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, hormone replacement after endocrinopathy).
* Subject has been administered prior chemotherapy or immunotherapy at any time, and any with radiation therapy within 4 weeks prior to time of consent or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to previously administered agent.
1. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
2. Subjects with endocrinopathy which is adequately controlled with hormone replacement therapy are an exception to this criterion and may qualify for the study.
* If subject underwent major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
* Subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
* A known or underlying medical condition that, in the opinion of the investigator could make the administration of study drug hazardous to the subject or could adversely affect the ability of the subject to comply with or tolerate study therapy.
* Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with the study drugs.
* Subjects who are unable to undergo venipuncture and/or tolerate venous access
* Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days prior to initiation of study drug therapy
* Subjects who are on immunosuppressive therapy (systemic steroids 10mg and more daily use)
* Prisoners or subjects who are involuntarily incarcerated
* Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
* Inability to comply with restrictions and prohibited activities and treatments

Contacts and Locations

Study Contact

Julie Urban, PhD

CONTACT

412-623-7396

urbanj2@upmc.edu

Principal Investigator

Jason Luke, MD, FACP

PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Study Locations (Sites)

University of Chicago Medical Center

Chicago, Illinois, 60637

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

Collaborators and Investigators

Sponsor: Jason J. Luke, MD

Jason Luke, MD, FACP, 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 Date2021-11-29

Study Completion Date2027-05-31

Study Record Updates

Study Start Date2021-11-29

Study Completion Date2027-05-31

Terms related to this study

Keywords Provided by Researchers

Anti-PD-1 monoclonal antibody (mAb)
Anti-IL-8
Stereotactic Body Radiotherapy (SBRT)

Additional Relevant MeSH Terms

Melanoma
Unresectable Solid Tumors
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Nivolumab