Study of Combined Ionizing Radiation and Ipilimumab in Metastatic Non-small Cell Lung Cancer (NSCLC)

NCT02221739 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 14-00208
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

lung cancer; NSCLC; lung; cancer; radiation; immunotherapy; metastatic

Outcome Measures

Primary Outcomes (1)

• 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.

  3 weeks - 6 months post treatment

Secondary Outcomes (1)

• 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

  3 weeks - 6 months post-treatment

Study Arms (1)

Ipilimumab + radiotherapy

EXPERIMENTAL

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)

Interventions

Ipilimumab DRUG

Also known as: Yervoy

Ipilimumab + radiotherapy

Radiotherapy (IMRT or 3-D CRT) RADIATION

Ipilimumab + radiotherapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document;
• Histologic diagnosis of metastatic NSCLC;
• Any Kras or EGFR status is permitted;
• Patients must have at least two distinct measurable metastatic sites, with one of at least 1 cm or larger in its largest diameter. Patients may have additional non-measurable metastatic lesions (e.g., bone metastases);
• Patients must have prior treatment with at least one line of therapy for metastatic NSCLC. Any prior therapy is permitted except prior therapy with ipilimumab;
• An interval of 2 weeks from last previous therapy is required;
• Patients must have adequate organ and marrow function as defined by initial laboratory tests:
• WBC ≥ 2000/uL
• ANC ≥ 1000/uL
• Platelets ≥ 50 x 103/uL
• Hemoglobin ≥ 8 g/dL
• Creatinine ≤ 3.0 x ULN
• AST/ALT ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
• Bilirubin ≤ 3.0 x ULN (except patients with Gilbert's Syndrome, who must have a total bilirubin ≤ 3.0 mg/dL);
• Performance status ECOG 0-1;

You may not qualify if:

• Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
• Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, progressive systemic sclerosis \[scleroderma\]), systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\];
• Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea;
• Concomitant therapy with any of the following: Interleukin-2 (IL-2), interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids;
• Prior therapy with ipilimumab or another anti-CTLA-4 antagonist;
• Women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 8 weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding;
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

Sponsors & Collaborators

• NYU Langone Health: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

NYU Clinical Cancer Center

New York, New York, 10016, United States

Location

NYU Langone Medical Center, Tisch Hospital

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

Ipilimumab; Radiotherapy; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted

Limitations and Caveats

50 dynamic changes of T cell clones in blood were the strongest response predictors, confirming 51 pre-clinical mechanistic data.

Results Point of Contact

• Title: Silvia Formenti, M.D.
• Organization: Weill Cornell Medical College

formenti@med.cornell.edu

646-962-4065

Study Officials

• Abraham Chachoua, MD

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: August 20, 2014
• Study Start: July 1, 2014
• Primary Completion: April 15, 2015
• Study Completion: October 27, 2015
• Last Updated: May 11, 2020
• Results First Posted: November 22, 2019

Record last verified: 2020-04

Locations

US (2)