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

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Nivolumab

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ari M Vanderwalde

This phase II trial studies how well ipilimumab with or without nivolumab work in treating patients with melanoma that is stage IV or stage III and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. To compare progression free survival (PFS) of patients with advanced melanoma refractory to an anti-PD-1 or anti-PD-L1 agent, treated with combination therapy ipilimumab plus nivolumab versus ipilimumab alone.

SECONDARY OBJECTIVES:

I. To estimate difference in T-cell infiltrate between on-study biopsy samples of patients who respond to combination therapy (including confirmed and unconfirmed, complete and partial response per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1, in each treatment arm).

II. To evaluate the objective response rate (ORR), defined as confirmed complete or partial response per RECIST 1.1, in each treatment arm.

III. To evaluate the overall survival (OS) of patients in each treatment arm. IV. To evaluate the toxicity profile of patients in each treatment arm.

TRANSLATIONAL OBJECTIVES:

I. To assess the marginal prognostic value of baseline T-cell density, T-cell receptor (TCR) clonality, mutational load, messenger ribonucleic acid (mRNA) and other phenotypical expression levels, and circulating tumor deoxyribonucleic acid (DNA) in terms of response.

II. To assess the joint prognostic value of T-cell density, TCR clonality, and mutational load, mRNA and other phenotypical expression levels, and circulating tumor DNA in terms of response.

III. To identify T-cell poor subtype(s) that are associated with response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 1 year.

Testing Treatment With Ipilimumab and Nivolumab Compared to Treatment With Ipilimumab Alone in Advanced Melanoma

A Phase II Randomized Study of Nivolumab (NSC-748726) With Ipilimumab (NSC-732442) or Ipilimumab Alone in Advanced Melanoma Patients Refractory to an Anti-PD1 or Anti-PD-L1 Agent

Progression-free survival (PFS) is defined as the time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact. Progression is defined as either 20% increase in the sum of diameters of target measurable lesions, unequivocal progression of non-measurable disease in the opinion of the treating physician, appearance of any new lesion, or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.

Will estimate the quantitative change in CD8+ expression from baseline to day 28 on-study between patients who eventually respond and patients who do not respond in the Nivolumab + Ipilimumab arm.

The overall objective response rate is defined as percentage of participants that achieved confirmed and unconfirmed, complete and partial responses. Complete response is defined as complete disappearance of all target and non-target lesions, no new lesions, and no disease related symptoms. Partial response applies only to patients with at least one measurable lesion and is defined as \>= 30% decrease of the sum of diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions.

Overall survival is defined as the time from randomization to the date of death from any cause.

Only adverse events that are possibly, probably or definitely related to study drug are reported. Adverse Events (AEs) are reported by CTCAE Version 4.0.

National Cancer Institute (NCI)

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only eligible participants who received protocol treatment were evaluated for adverse events (91 total; 23 on the ipilimumab arm; 68 on the nivolumab + ipilimumab arm), whereas all eligible participants were evaluated for all-cause mortality (92 total; 23 on the ipilimumab arm; 69 on the nivolumab + ipilimumab arm).

Active Comparator: Arm I (ipilimumab)

Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Experimental: Arm II (nivolumab, ipilimumab)

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Nivolumab + Ipilimumab

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

White

Black

Asian

Unknown

Race/Ethnicity, Customized

Zubrod performance status scores range from 0 to 2, with higher scores reflecting greater disability.

0: Fully active, able to carry on all pre-disease performance without restriction.

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
2. Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.

Zubrod Performance Status Score

Elevated

Normal

LDH Not Done

Blood lactate dehydrogenase (LDH) levels were measured and classified as either elevated or normal.

Stage III

Stage IV

Participants' disease stage was classified according to the AJCC melanoma classification. Stage III: Any T, N3, M0. Stage IV: Any T, Any N, M1.

AJCC Melanoma Classification

No prior adjuvant therapy

Adjuvant PD-1

Adjuvant BRAF/MEK

Other Adjuvant Therapy

Prior Adjuvant Therapy

Adjuvant Therapy Only

Anti-PD-1 only

BRAF/MEK followed by PD-1

Other anti-PD-1 combination

Prior Metastatic Therapy

< 6 Months

>= 6 Months

Duration of prior anti-PD1/PD-L1 Therapy

Only eligible participants were assessed for baseline measures.

Melanoma Committee Statistician

The statistical design assumed exponential PFS with a median of 3.0 months on the ipilimumab group (null hypothesis). The study was powered to detect a change in median PFS to 6.0 months in the combination therapy group (corresponding to an HR of 0.50). A total of 84 participants (63 randomized to combination group and 21 to ipilimumab group) with 78 events (across both groups) would provide 89% power for a one-sided alpha of 10% using a log-rank test.

Only eligible participants were analyzed for PFS.

Progression Free Survival

Participants on the combination Nivolumab + Ipilimumab arm that responded to protocol therapy.

Responders

Non-Responders

All participants on the combination Nivolumab + Ipilimumab arm that were had biopsies available at baseline and four weeks after the start of protocol therapy.

Overall

There were 83 total participants with biopsies available; 76 with a baseline biopsy and 56 with a biopsy from 28 days after start of protocol therapy. This resulted in a total of 40 paired biopsies on both arms after excluding samples that could not be analyzed because of absence of tumor due or insufficient tumor cells. Our analysis population for this outcome measure includes the 29 participants on the combination Nivolumab + Ipilimumab arm that had an analyzable paired biopsy.

Change in CD8+ Expression

All eligible participants were considered analyzable for this endpoint.

Overall Objective Response Rate

All eligible participants were included in the overall survival analysis.

Overall Survival

Acute kidney injury

Adrenal insufficiency

Alanine aminotransferase increased

Alkaline phosphatase increased

Anemia

Anorexia

Arthralgia

Aspartate aminotransferase increased

Atrial fibrillation

Autoimmune disorder

Blood bilirubin increased

Colitis

Colonic perforation

Dehydration

Diarrhea

Disseminated intravascular coagulation

Endocrine disorders - Other, specify

Enterocolitis

Fatigue

Fever

Hyperglycemia

Hypernatremia

Hypocalcemia

Hypokalemia

Hyponatremia

Hypophosphatemia

Hypotension

Hypothyroidism

Infections and infestations - Other, specify

Lung infection

Lymphocyte count decreased

Metabolism and nutrition disorders - Other, specify

Nausea

Pain

Pruritus

Rash maculo-papular

Syncope

Uveitis

Vomiting

Participants who received at least one dose of protocol treatment

Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Active Comparator: Arm I (ipilimumab)

Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Experimental: Arm II (nivolumab, ipilimumab)

Patients receive nivolumab 1 mg/kg IV over 30 minutes and ipilimumab 3 mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab 480 mg IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Overall Study

Symptoms and General Pathology

Digestive System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Esophageal Neoplasms

Carcinoma

Adenocarcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Transitional Cell

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Carcinoma, Renal Cell

Carcinoma, Hepatocellular

Esophageal Squamous Cell Carcinoma

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Disease Attributes

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Squamous Cell

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Head and Neck Neoplasms

Esophageal Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Esophageal Cancer

Transitional Cell Carcinoma

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Patients receive nivolumab SC on day 1 of each cycle. Cycles repeat every 28 days in clinic for 2 cycles, then at home by a HHNP for 4 cycles, followed by either in-clinic or at-home administration for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive in-home visits by a home health nurse and undergo remote patient monitoring including vital sign measurements and condition-specific symptom assessments throughout study.

Receive in-home visits by a home health nurse

Home Health Encounter

Patient Monitoring

Questionnaire Administration

Clinical Trials Referral Office

Roxana S. Dronca, M.D.

This phase II trial compares the impact of subcutaneous (SC) nivolumab given in an in-home setting to an in-clinic setting on cancer care and quality of life. Currently, most drug-related cancer care is conducted in clinic type centers or hospitals which may isolate patients from family, friends and familiar surroundings for many hours per day. This separation adds to the physical, emotional, social, and financial burden for patients and their families. Traveling to and from medical facilities costs time, money, and effort and can be a disadvantage to patients living in rural areas, those with low incomes or poor access to transport. Studies have shown that cancer patients often feel more comfortable and secure being cared for in their own home environments. SC nivolumab in-home treatment may be safe, tolerable and/or effective when compared to in-clinic treatment and may reduce the burden of cancer and improve the quality of life in cancer patients.

PRIMARY OBJECTIVE:

I. Determine the change in patient-reported rating of Cancer Connected Access and Remote Expertise (CARE) after 8 weeks in clinic compared to the same rating after 8 weeks at home.

SECONDARY OBJECTIVES:

I. Evaluate patient preference for location of cancer treatment administration, in the clinic or in the home.

II. Longitudinally assess patient-reported function and global health/quality of life.

III. Longitudinally assess patient-reported symptoms. IV. Assess the safety of cancer directed therapy when administered at home by a home health provider with remote patient monitoring and command center support.

V. Describe emergency room visits and hospitalizations over the course of the study.

VI. Describe overall survival (data collected out to 1 year).

TERTIARY OBJECTIVE:

I. Assess the cost outcomes related to patient treatment in the clinic or in the home.

OUTLINE:

Patients receive nivolumab SC on day 1 of each cycle. Cycles repeat every 28 days in clinic for 2 cycles, then at home by a home health nursing provider (HHNP) for 4 cycles, followed by either in-clinic or at-home administration for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients receive in-home visits by a home health nurse, undergo remote patient monitoring including vital sign measurements and condition-specific symptom assessments throughout study.

After completion of study treatment, patients are followed up at days 30 and 100, then every 3 months for up to 1 year.

Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program

Pilot Single-Arm, Pragmatic Trial of In-Home Versus In-Clinic Subcutaneous Nivolumab Administration Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program

Measured using the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Cancer Care Survey assessing "your overall cancer care experience," answered on a scale of 0-10 where 0 is the worst experience possible and 10 is the best experience possible. The change in patient-reported rating of Cancer CARE after 8 weeks of in clinic care to the same rating after 8 weeks of at home care will be compared.

The proportion of patients who prefer care at home or express no preference will be computed and compared with the proportion of patients who prefer care in the clinic.

The proportion of patients who express comfort will be tabulated and a proportion greater than 70% will signify acceptance. Likert patient feedback questions and "Was It Worth It" questions will be described using frequencies and relative frequencies by arm. Numeric analog scale questions will be described using means and standard deviations and compared within patients (if applicable) using paired t-tests. Descriptive estimates at 24 weeks (after 8 weeks of in clinic and 16 weeks of at home care) will be generated throughout.

Patient-reported symptoms will be measured using the Patient Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). In this study, PRO-CTCAE items were chosen based on common symptoms experienced across cancer patients and side effects common with nivolumab. A free-text item will also be included for patients to report other symptoms as willing. Adverse events (AEs) will be tabulated during the 8 weeks in clinic, and during the 8 weeks at home, compared between arms and summarized over the 24 weeks.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing Treatment With Ipilimumab and Nivolumab Compared to Treatment With Ipilimumab Alone in Advanced Melanoma	NCT03033576	Clinical Stage ... Clinical Stage ... Melanoma of Unk... Mucosal Melanom... Unresectable Cu... Unresectable Me...	Ipilimumab Nivolumab	18 Years -	National Cancer Institute (NCI)
Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program	NCT06265285	Advanced Esopha... Advanced Renal ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Esophageal Carc... Gastroesophagea... Hepatocellular ... Locally Advance... Lung Non-Small ... Malignant Solid... Metastatic Colo... Metastatic Cuta... Metastatic Esop... Metastatic Head... Metastatic Urot... Recurrent Esoph... Recurrent Head ... Renal Cell Carc... Stage III Renal... Stage IV Colore... Stage IV Cutane... Stage IV Renal ... Unresectable Cu... Unresectable Es... Urothelial Carc...	Home Health Enc... Nivolumab Patient Monitor... Questionnaire A...	18 Years -	Mayo Clinic
Binimetinib and Nivolumab for the Treatment of Locally Advanced Unresectable or Metastatic BRAF V600 Wildtype Melanoma	NCT04375527	Clinical Stage ... Clinical Stage ... Locally Advance... Metastatic Cuta... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Unresectable Cu...	Binimetinib Nivolumab Questionnaire A...	18 Years -	Jonsson Comprehensive Cancer Center
Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program	NCT06265285	Advanced Esopha... Advanced Renal ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Esophageal Carc... Gastroesophagea... Hepatocellular ... Locally Advance... Lung Non-Small ... Malignant Solid... Metastatic Colo... Metastatic Cuta... Metastatic Esop... Metastatic Head... Metastatic Urot... Recurrent Esoph... Recurrent Head ... Renal Cell Carc... Stage III Renal... Stage IV Colore... Stage IV Cutane... Stage IV Renal ... Unresectable Cu... Unresectable Es... Urothelial Carc...	Home Health Enc... Nivolumab Patient Monitor... Questionnaire A...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for unresectable cutaneous melanoma