Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Pembrolizumab

Antibodies

Cyclophosphamide

Molgramostim

Sargramostim

Ipilimumab

Immunoglobulins

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Efficacy of Cryosurgical Freezing and Multiplex Immunochemotherapy as determined by overall response rate of radiographic changes according to iRECIST criteria.

Keytruda (pembrolizumab): PD-1 inhibitor antibody

Injectable 50mg/mL, only 2 mL injected.

Keytruda Injectable Product

Yervoy (ipilimumab): Anti-CTLA-4 antibody

Injectable 5mg/mL, only 2 mL injected.

Yervoy Injectable Product

Injectable 250mg/m2, only 1 mL injected. Oral low dose cyclophosphamide: 50mg once daily pill for 5 days prior to first treatment, 3 days prior to 2nd and 3rd treatment.

Cytoxan

Cryosurgery, also known as cryoablation, for metastatic cancer works by freezing the cancer cells inside the tumor. Cryoablation will release intact antigens to prime the immune system.

Cryosurgical freezing (cryosurgery)

Daily injection administered subcutaneously. 250 mcg daily injections for a total of 25 days post after each treatment.

GM-CSF Injectable

David G Bostwick, M.D., M.B.A.

This study seeks to estimate the potential efficacy of the study treatment, as well as the occurrence of adverse events.

Cryosurgical freezing (limited to 1.5 cm diameter single freeze within the cancer (up to two cancer sites selected and treated)) will release intact antigens to prime the immune system. The study treatment immunotherapeutic drugs (PD-1 inhibitor monoclonal antibody nivolumab or pembrolizumab and anti-CTLA-4 monoclonal antibody ipilimumab, and low-dose cyclophosphamide) will then be sequentially injected directly into each of the treated cancer sites immediately following cryosurgical freezing. These injections will be performed in combination with collagen (Helitene) to improve drug containment at the site of injection for improved local effect rather than rapid disbursement and dilution throughout adjacent interstitial spaces, as well as sustained drug delivery over time rather than a burst-release pattern. Prior to study treatment, oral low dose cyclophosphamide will be given. Post-treatment, daily subcutaneous low-dose GM-CSF injections will also be administered subsequently. It is speculated that neoantigens released from the cryoablated necrotic cancer will be available in the vicinity of the cryosurgical freezing field immediately following the procedure. Immature dendritic cells attracted to the injection site will internalize neoantigens to become activated to recognize cancer-specific antigenic proteins. The activated dendritic cells will recruit killer T-cells to the injection site to attack cancer cells, and then migrate through the lymphatic system to sites of metastases, targeting cancer-specific neoantigens and recruiting more killer T-lymphocytes to destroy other cancer cells harboring the precise antigenic epitopes (abscopal (bystander) effect). In this way, dendritic cells are capable of initiating cell-mediated systemic immune response in combination with cytotoxic killer T-cells. Regulatory T lymphocytes, which have been implicated in dampening or halting cell-mediated, antigen-specific immune responses, will be selectively depleted by anti-CTLA-4 monoclonal antibodies, low-dose cyclophosphamide, and metronomic GM-CSF. Intra-tumoral injection of the immunotherapeutic medications assists in stimulating and harnessing the local and systemic immune response. GM-CSF prolongs the immune response. Using this combination of therapies, referred to as AbscopalRx5001, it is thought that a clinically significant systemic anti-cancer immune response might be elicited. Intra-tumoral injection of drugs will likely offer fewer side effects than systemic therapy.

Male or female subjects greater than 18 years of age with histologically- proven metastatic cancer with at least one imaging- or histologically- proven metastases to lymph nodes, bone, or soft tissue.

A Phase 2 Trial for Patients With Metastatic Solid Cancer

A Phase 2 Trial of Cryosurgical Freezing and Multiplex Immunochemotherapy in Patients With Metastatic Solid Cancer

rPFS as determined with both RECISTS1.1 and iRECIST criteria.

Best overall response of confirmed PR or CR by independent radiology review

Time to cancer progression is measured from the date of first study treatment until the date of cancer progression.

Incidence of adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Data will be collected for the design of future studies.

Each of the endpoints will be evaluated after stratifying for site of cancer origin, histologic type, and cancer grade (W.H.O. grading)

Efficacy of Cryosurgical Freezing and Multiplex Immunochemotherapy as determined by RECIST1.1 criteria

Rampart Health, L.L.C.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Adenocarcinoma

Prostatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Nivolumab

Immunomodulating Agents

Cryosurgical freezing and intratumoral combination immunotherapy as determined by the proportion of patients achieving serum PSA decline from baseline of at least 50%.

Opdivo (nivolumab): PD-1 inhibitor antibody

Injectable 10mg/mL, only 1 mL injected.

Opdivo Injectable Product

Yervoy (ipilimumab): Anti-CTLA-4 antibody

Injectable 5mg/mL, only 1 mL injected.

Cytoxan (cyclophosphamide): Chemotherapy agent

Both Injectable and Oral low dose:

Injectable 250mg/m2, only 1 mL injected. Oral low dose cyclophosphamide: option of either 50mg once daily pill or 25mg twice daily pill for two weeks on, then two weeks off, then two weeks on again.

Cryosurgery, also known as cryoablation, for prostate cancer works by freezing the cancer cells inside the prostate gland. Cryoablation will release intact antigens to prime the immune system.

David G Bostwick, M.D.,M.B.A.

This study seeks to estimate the occurrence of adverse events related to the study treatment (Cryosurgical freezing and Intratumoral Combination Immunotherapy), as well as determine the potential efficacy.

Cryosurgical freezing will release intact antigens to prime the immune system. The study treatment immunotherapeutic drugs (PD-1 inhibitor monoclonal antibody nivolumab and anti-CTLA-4 monoclonal antibody ipilimumab, and cyclophosphamide) will then be sequentially injected directly into the cancer immediately following cryosurgical freezing. Oral low-dose cyclophosphamide will also be administered subsequently. It is speculated that neoantigens released from the cryoablated necrotic cancer will be available in the vicinity of the cryosurgical freezing field immediately following the procedure. Immature dendritic cells attracted to the injection site will internalize neoantigens to become activated to recognize cancer-specific antigenic proteins. The activated dendritic cells will recruit killer T-cells to the injection site to attack cancer cells, and then migrate through the lymphatic system to sites of metastases, targeting cancer-specific neoantigens and recruiting more killer T-lymphocytes to destroy other cancer cells harboring the precise antigenic epitopes (abscopal (bystander) effect). In this way, dendritic cells are capable of initiating cell-mediated systemic immune response in combination with cytotoxic killer T-cells. Regulatory T lymphocytes, which have been implicated in dampening or halting cell-mediated, antigen-specific immune responses, will be selectively depleted by anti-CTLA-4 monoclonal antibodies and low-dose cyclophosphamide. Intratumoral injection of the immunotherapeutic medications assists in stimulating and harnessing the local and systemic immune response. Oral cyclophosphamide prolongs the immune response. Using this combination of therapies, referred to as AbscopalRx1001, it is thought that a clinically significant systemic anti-cancer immune response might be elicited. Intratumoral injection of drugs will likely offer fewer side effects than systemic therapy.

Male subjects greater than 18 years of age with histologically-proven cancer of the prostate with at least one imaging- or histologically -proven metastasis to lymph nodes or bone.

A Phase 2 Trial for Men With Metastatic Prostatic Adenocarcinoma

A Phase 2 Trial of Cryosurgical Freezing and Intratumoral Combination Immunotherapy in Men With Metastatic Prostatic Adenocarcinoma

Efficacy of cryosurgical freezing and intratumoral combination immunotherapy as determined by RECIST1.1 criteria. Overall response rate as determined by PCWG3 using RECIST1.1 radiographic response.

Radiographic progression-free survival (rPFS) rPFS as determined by PCWG3 with both RECISTS1.1 and iRECIST criteria.

Time to Prostate Specific Antigen (PSA) progression (TTPP) Time to PSA progression is measured from the date of first study treatment until the date of PSA progression according to PCWG3 criteria.

Overall survival: Number and percent of participants that are alive.

Incidence of AEs/SAEs: An AE is any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity. Incidence was defined as the number of participants who experienced an adverse event within their period of participation in this study. Incidence of adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

Primary Endpoint: Efficacy of cryosurgical freezing and intratumoral combination immunotherapy as determined by the proportion of patients achieving serum PSA decline from baseline of at least 50%.

Efficacy of cryosurgical freezing and intratumoral combination immunotherapy as determined by iRECIST criteria. Overall response rate as determined by PCWG3 using iRECIST radiographic response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 2 Trial for Patients With Metastatic Solid Cancer	NCT04713371	Metastatic Canc...	Keytruda Inject... Yervoy Injectab... Cytoxan Cryosurgical fr... GM-CSF Injectab...	18 Years -	Rampart Health, L.L.C.
A Phase 2 Trial for Patients With Metastatic Solid Cancer	NCT04713371	Metastatic Canc...	Keytruda Inject... Yervoy Injectab... Cytoxan Cryosurgical fr... GM-CSF Injectab...	18 Years -	Rampart Health, L.L.C.
A Phase 2 Trial for Men With Metastatic Prostatic Adenocarcinoma	NCT04090775	Metastatic Pros...	Opdivo Injectab... Yervoy Injectab... Cytoxan Cryosurgical fr...	18 Years -	Rampart Health, L.L.C.

Spots Global Cancer Trial Database for cryosurgical freezing (cryosurgery)