A Phase 1/2 interventional study of Ipilimumab and Radiotherapy (IMRT or 3-D CRT) in Non-small Cell Lung Cancer (NSCLC), sponsored by NYU Langone Health. Completed at 2 sites in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2020-05-11.
Sponsored by NYU Langone Health · Phase 1/2, Interventional, and Treatment
The purpose of this study is to investigate how effective and how safe the combination of radiation therapy and an investigational medication targeting the immune system known as Ipilimumab in the treatment of metastatic non-small cell lung cancer (NSCLC).
The investigators would like to see if this combination of radiation and Ipilimumab can stimulate the body's immune system to stop the growth of tumors that are outside the field of radiation. The investigators would like see if using this combination of radiation therapy with Ipilimumab could help the body reject the patient's own tumor or at least help their immune system to maintain the disease stable and/or slow its growth.
Radiation therapy (RT) is currently a standard procedure for treatment of NSCLC. Ipilimumab is considered an investigational medication because it is not approved by the Food and Drug Administration (FDA) for the treatment of NSCLC. Ipilimumab has been approved by the FDA for the treatment of metastatic melanoma.
Research Hypothesis:
Objective 1: Evaluate the safety and therapeutic efficacy of anti-cytotoxic T-lymphocyte-associated protein -4 mono clonal Antibody (anti-CTLA-4 mAb) and concurrent local RT in NSCLC patients with metastatic disease.
An open label phase II trial will evaluate the preliminary efficacy of the combination of Ipi and RT, applied to a single metastatic site. Efficacy is measured with respect to systemic tumor responses (abscopal response, outside the field of therapy) defined by immune-related Response Criteria (irRC) in all non-irradiated measurable lesions, as a demonstration of an effective anti-tumor immune response. Secondary endpoints include local response in the RT treated tumor, progression free survival, and overall survival.
Objective 2: Determine the effects of RT and anti-CTLA-4 mAb on development of anti-tumor immunity.
The investigators hypothesize that RT will convert the irradiated tumor into an in situ vaccine and elicit an endogenous tumor-specific cellular and humoral immune response, which in the presence of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade will promote immune-mediated destruction of the irradiated and abscopal metastases. Pre- and post-treatment tumor biopsies will be examined for changes in immune contexture, and blood for evidence of emerging anti-tumor immune responses. Associations with clinical response will be explored.
7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.
This study's enrollment of 39 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.
Browse Lung Neoplasms studies →NYU Langone Health is the lead sponsor of 1,391 studies on the registry; 254 are open to participants now.
Of its 227 completed or terminated interventional studies of FDA-regulated products, 191 (84%) have results posted.
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Patients must have adequate organ and marrow function as defined by initial laboratory tests:
Exclusion Criteria:
Patients receive ipilimumab (Ipi) 3mg/kg i.v. over 90 minutes, within 24 hours of starting radiotherapy (RT) to the biopsied lesion, 6 Gy x5, later changed to 9.5 Gy x3 (conformally or by intensity modulated RT (IMRT) with image guidance to maximally spare normal tissue). Ipilimumab is repeated on days 22, 43 (for patients who consent to the first biopsy), and 64. Repeat biopsy is performed between day 22-29, and patients are re-imaged between day 81-88 and evaluated for response (defined as an objective response by irRC of the measurable metastatic sites outside the radiation field).
Drug: Ipilimumab · Radiation: Radiotherapy (IMRT or 3-D CRT)
Also known as: Yervoy
Therapeutic Efficacy of Anti-CTLA-4 mAb and Concurrent Local RT in NSCLC Patients With Metastatic Disease.
Tumor Response will be evaluated using the irRC best response (Partial Response (PR) + Complete Response (CR)). Modified WHO criteria will be used for measurement of tumors. The irradiated lesion will be excluded from the assessment of response.
Time frame: 3 weeks - 6 months post treatment
Number pf Patients With Objective Radioactive Responses to Measure the Effects of RT and Anti-CTLA-4 mAb on Development of Anti-tumor Immunity Measured by T Cell Clone Frequency
The study uses a comprehensive approach to analyze immunological changes that reflect both local and systemic responses, and investigate both general immune activation as well as tumor antigen-specific T- and B-cell responses. The activity of anti-CTLA-1 mAb is thought to be mainly dependent on modulating the quantity and quality of T-cells in cancer patients. A highly extensive analysis of the Cluster of differentiation 4 + (CD4+) and cluster of differentiation 8 + (CD8+) T-cell subsets will be characterized by multi-color flow Cytometry. To facilitate these analyses, serial blood samples will be collected for serum and peripheral blood mononuclear cells (PBMC) at different time points, where, a part of these samples will be used for DNA/RNA extraction. Optional tissue biopsies will be obtained from consenting patients.Tumor tissue will be tested for expression of seven antigens frequently expressed in NSCLC.
Time frame: 3 weeks - 6 months post-treatment
| Milestone | Ipilimumab + Radiotherapy |
|---|---|
| Started | 39 |
| Completed | 21 |
| Not completed | 18 |
Tumor Response will be evaluated using the irRC best response (Partial Response (PR) + Complete Response (CR)). Modified WHO criteria will be used for measurement of tumors. The irradiated lesion will be excluded from the assessment of response.
| Participants | Ipilimumab + Radiotherapy |
|---|---|
| Therapeutic Efficacy of Anti-CTLA-4 mAb and Concurrent Local RT in NSCLC Patients With Metastatic Disease. | 7 |
The study uses a comprehensive approach to analyze immunological changes that reflect both local and systemic responses, and investigate both general immune activation as well as tumor antigen-specific T- and B-cell responses. The activity of anti-CTLA-1 mAb is thought to be mainly dependent on modulating the quantity and quality of T-cells in cancer patients. A highly extensive analysis of the Cluster of differentiation 4 + (CD4+) and cluster of differentiation 8 + (CD8+) T-cell subsets will be characterized by multi-color flow Cytometry. To facilitate these analyses, serial blood samples will be collected for serum and peripheral blood mononuclear cells (PBMC) at different time points, where, a part of these samples will be used for DNA/RNA extraction. Optional tissue biopsies will be obtained from consenting patients.Tumor tissue will be tested for expression of seven antigens frequently expressed in NSCLC.
| Participants | Ipilimumab + Radiotherapy |
|---|---|
| Objective Radiographic Responses | 7 |
| Complete Responses (CR) | 2 |
| Partial Responses (PR) | 5 |
Collected over 60 Months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ipilimumab + Radiotherapy | 17/39 (43.6%) | 19/39 (48.7%) | 39/39 (100%) |
| Event | Ipilimumab + Radiotherapy |
|---|---|
| DeathNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 19/39 |
| Event | Ipilimumab + Radiotherapy |
|---|---|
| FatiguePsychiatric disorders | 30/39 |
| PruritisGeneral disorders | 17/39 |
| AnorexiaPsychiatric disorders | 15/39 |
| RashGeneral disorders | 13/39 |
| DiarrheaGastrointestinal disorders | 11/39 |
| DyspneaPsychiatric disorders | 9/39 |
| Alkaline PhosphotaseHepatobiliary disorders | 6/39 |
| ALTHepatobiliary disorders | 6/39 |
| AnemiaBlood and lymphatic system disorders | 6/39 |
| ASTHepatobiliary disorders | 5/39 |
| Age, Customized(years) | Ipilimumab + Radiotherapy |
|---|---|
| Age | 68 (48 to 97) |
| Sex: Female, Male(Participants) | Ipilimumab + Radiotherapy |
|---|---|
| Gender — Female | 23 |
| Gender — Male | 16 |
| Race and Ethnicity Not Collected(Participants) | Ipilimumab + Radiotherapy |
|---|
| Region of Enrollment(Participants) | Ipilimumab + Radiotherapy |
|---|---|
| United States | 39 |
| Histology(Participants) | Ipilimumab + Radiotherapy |
|---|---|
| Adenocarcinoma | 34 |
| Squamous Cell Carcinoma | 3 |
| Sarcomatoid | 1 |
| Neuroendocrine | 1 |
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