Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immunologic Factors

Immune Checkpoint Inhibitors

This is standard of care arm: induction with 4 cycles (21 days each) of Ipilimumab and nivolumab followed by continuation with nivolumab alone every month X1 year (13 doses).

This includes induction with 4 cycles of ipilimumab and nivolumab X 4 cycles followed by continuation with nivolumab alone every month for 1 year as in standard of care arm. Each induction cycle is 21 days and includes ipilimumab on day 1 plus nivolumab on day 1. In addition, patients will receive 4 weekly doses of Rituxan (first dose intravenously and then 3 weekly doses subcutaneously). First dose of Rituxan will be administered one week following the start of cycle 1 of ipilimumab and nivolumab. All treatments will have a +/-3 business day window for administration.

Receive standard of care nivolumab therapy

Rituximab and Hyaluronidase Human

Receive standard of care ipilimumab therapy

Kavita Dhodapkar, MD

This phase II trial studies whether rituximab and hyaluronidase human (Rituxan Hycela) can prevent immune related adverse events in participants with stage III-IV melanoma that cannot be removed by surgery who are undergoing nivolumab and ipilimumab therapy.

PRIMARY OBJECTIVE:

I. To compare rates for grade 3-4 immune-related adverse event (IRAE)s in the first 6 months in patients treated with combination checkpoint blockade (CCB) therapy (anti-CTLA4 and anti-PD1) as a part of standard of care for advanced melanoma who are treated with a single course of 4 weekly doses of rituximab and hyaluronidase human (Rituxan) therapy versus those who are not treated with Rituxan.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability (in terms of Rituxan-related adverse events) in patients with melanoma receiving CCB.

II. To compare objective response rate in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

III. To compare 1 year overall and progression-free survival in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

IV. To compare changes in cluster of differentiation 21lo (CD21lo) B cells in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

V. To compare changes in T cells in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM A: Participants receive standard of care ipilimumab and nivolumab therapy.

ARM B: Participants receive standard of care ipilimumab and nivolumab therapy. On day 2 of each cycle, participants also receive rituximab and hyaluronidase human intravenously (IV) or subcutaneously (SC) weekly starting week 1 for 4 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up for 4 weeks.

Rituximab and Hyaluronidase Human in Patients With Advanced Melanoma Undergoing Nivolumab and Ipilimumab Therapy

A Randomized Phase 2 Study of Rituxan Hycela in Patients With Advanced Melanoma Undergoing Combination Immune Checkpoint Blockade With Nivolumab and Ipilimumab

All patients will be evaluable for toxicity from the time of their first treatment with ipilimumab/nivolumab. Investigators will review the toxicities, grade, and attribute each toxicity.

Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related (ir)RECIST. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. Patients who exhibit objective disease progression prior to the end of cycle 1 will also be considered evaluable.

Overall survival is defined as the duration of time from start of treatment to time of death or last follow-up, whichever occurs first.

PFS is defined as the duration of time from start of treatment to time of progression or death or last follow-up, whichever occurs first.

Genentech, Inc.

Emory University

Principal Investigator

Vaccines

Immunomodulating Agents

Adjuvants, Immunologic

Therapeutic Classification:

* Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator

Route of Administration:

* Intratumoral injection of cutaneous, subcutaneous or nodal lesions

Mechanism of Action:

* Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface.

Physiological Effect:

* This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions.

Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).

IFx-Hu2.0

Joseph Markowitz, MD, PhD

Six patients will receive IFx-Hu2.0 on an outpatient basis at a single time point in a single lesion, two lesions, or three lesions, as a monotherapy (a maximum of three lesions could be injected). These patients will be assessed for any immediate adverse reactions and at Week 4 (Day 28+/-7 business days for any delayed adverse events.

Six male and/or female adult patients (greater than or equal to 18 years old), of any ethnicity and race, with unresectable stage III or stage IV cutaneous melanoma with accessible lesions, will be eligible for enrollment and treatment with IFx-Hu2.0.

To be eligible for this study, patients with unresectable metastatic disease must have failed, refused or been deemed not candidates for at least one form of systemic anti-PD-1-based immunotherapy as well as BRAF inhibition, if BRAF V600 mutated. Talimogene laherparepvec (IMLYGIC®) is indicated for local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Therefore, patients with unresectable cutaneous, subcutaneous, and nodal melanoma lesions recurrent after initial surgery must have failed, refused or been deemed not candidates for talimogene laherparepvec to be eligible for this study.

Enrollees will receive IFx-Hu2.0 at a single time point. Depending on the number of accessible lesions, a patient could receive up to three doses across three lesions (one dose per lesion). Forty milliliters of peripheral blood will be collected from these patients prior to treatment administration and at the follow-up visit four weeks later. The target dose will be 100 μg of plasmid DNA per lesion injected at a final dose volume of 200 μL per lesion. To allow for the observation of any acute toxicity in the first subject enrolled and prevent any occurrence of excessive toxicities in subsequent subjects, the first subject enrolled will receive a single dose of IFx-Hu2.0. Subsequent subjects will be administered the product after at least seven days. Beyond the first subject, the maximum number of lesions to be injected at any given time point in the study phase proposed is three lesions. These samples will be used to perform complete blood counts (CBC) and clinical chemistry tests. A urine sample will be obtained for urinalysis for protein and blood at the same frequency. Blood samples will be drawn for immune response evaluation as well. At the end of the study period, a biopsy of the lesion injected and a non-injected lesion (if applicable) will be collected. If the patient has a response to therapy, the patient will have the option of continuing the study at three-week intervals so long as they have not progressed. Optional tumor biopsies and peripheral blood collections may be obtained on subsequent treatment cycles.

pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

Phase 1 Study Using a Plasmid DNA Coding for Emm55 Streptococcal Antigen in Patients With Unresectable Stage III or Stage IV Cutaneous Melanoma

Safety was reported using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Feasibility was defined as the ability to treat at least five of the six patients enrolled without drug-related dose-limiting toxicity (DLT).

Evaluation of response rate and assessment of the antitumor immune responses induced by IFx-Hu2.0 per RECIST v1.1 for target lesions.

Complete Response (CR), Disappearance of all target lesions. Partial Response (PR), ≥ 30% decrease in the sum of the longest diameters of target lesions compared with baseline.

Stable Disease (SD), Neither sufficient shrinkage to qualify for partial or complete response (CR or PR) nor sufficient increase to qualify for progressive disease (PD).

Progressive Disease (PD), Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

H. Lee Moffitt Cancer Center and Research Institute

TuHURA Biosciences, Inc.

Therapeutic Classification:

* Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator

Route of Administration:

* Intratumoral injection of cutaneous, subcutaneous or nodal lesions

Mechanism of Action:

* Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface.

Physiological Effect:

* This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions.

IFx-Hu2.0: Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).

IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Stage III: tumor no more than 2mm thick and could be ulcerated. Cancer has spread to 1-3 nearby nodes. It has not spread to distant parts of the body.

Stage IIIC: tumor no more than 2mm thick with 1-3 macroscopic node metastases and an ulcerated primary melanoma. Patients with satellite(s)/in-transit metastases, or any patient with nodal disease regardless of ulceration status.

Stage IV: tumor of any thickness and could be ulcerated. Cancer could have spread to nearby nodes. It has spread to distant nodes or to organs.

Note: lesser stages correlate with improved outcomes.

AJCC Clinical Staging

James Bianco, MD - Chief Executive Officer

Participants Analyzed

Serious Adverse Events (SAEs)

Dose Limiting Toxicity (DLT)

The data analysis is described to assess the safety of the injection of the study agent in six patients the intention-to-treat (ITT) approach will be used for response to treatment data analysis of this trial (secondary objective).

Number of Participants With Serious Adverse Events (SAEs) and/or Dose Limiting Toxicities (DLTs)

The intention-to-treat (ITT) approach will be used for response to treatment data analysis of this trial.

Antitumor Response Induced by IFx-Hu2.0 Per RECIST v1.1 for Target Lesions.

Overall Study

Pharmaceutical Solutions

Herbal and Botanical

Nutritional supplement Oncoxin-Viusid 25 mL in oral solution twice a day

Oncoxin-Viusid supplement before/during/after standard surgical and adjuvant treatment or chemotherapy.

Oncoxin-Viusid

Olaine R. Gray Lovio, Dr.

Malignant melanoma, responsible for 75% of deaths from skin cancer. Current therapeutic options have poor response, many adverse events and high costs. For this reason, a study with nutritional supplement Oncoxin-Viusid was carried out. According to previous studies, it has an antitumor, immunomodulatory effect and to potentiate the antiproliferative effect of standard chemotherapeutic agents in different locations and stages of cancer.

Performed at Manuel Fajardo Surgical Clinical University Hospital in Havana, Cuba from September 2014 to April 2018, following a proof of concept open label study, with no control group in 20 patients diagnosed histologically in Fajardo Hospital or Oncology Institute, as Melanoma, primary cutaneous stage IIB-IIIA. All received conventional surgical treatment and oral Oncoxin-Viusid (25 ml 2 times a day for one year), where it was also indicated adjuvant treatment or chemotherapy. All were evaluated monthly the first year and semesterly the second year. Complying with the provisions of the Helsinki Act.

Evaluation of Oncoxin-Viusid® in Cutaneous Melanoma

Evaluation of the Nutritional Supplement Oncoxin-Viusid® in the Treatment of 20 Patients With Cutaneous Melanoma in Stage IIB-IIIA

Calculated according to the method of Kaplan Meyer

Calculated according to the Kaplan Meyer method

Quality of life questionnaire of the EORTC: QLQ30

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rituximab and Hyaluronidase Human in Patients With Advanced Melanoma Undergoing Nivolumab and Ipilimumab Therapy	NCT03719131	Cutaneous Melan... Cutaneous Melan... Stage III Melan... Stage IIIA Skin... Stage IIIB Skin... Stage IIIC Skin... Stage IV Skin M... Unresectable Me...	Nivolumab Rituximab and H... Ipilimumab	18 Years -	Emory University
pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma	NCT03655756	Cutaneous Melan... Cutaneous Melan...	IFx-Hu2.0	18 Years -	TuHURA Biosciences, Inc.
Evaluation of Oncoxin-Viusid® in Cutaneous Melanoma	NCT03541148	Cutaneous Melan... Malignant Cutan... Cutaneous Melan...	Oncoxin-Viusid	18 Years -	Catalysis SL

Spots Global Cancer Trial Database for cutaneous melanoma, stage iii