Nivolumab and 177Lu-DOTA0-Tyr3-Octreotate for Patients With Extensive-Stage Small Cell Lung Cancer

NCT03325816 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2017-1081
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is being done to assess the safety and tolerability of study drugs, 177Lu-DOTA0-Tyr3-Octreotate (Lutathera) and nivolumab in subjects with small cell lung cancer or advanced or inoperable neuroendocrine tumor of the lung that has overexpressed somatostatin receptors (SSRT). Lutathera is an investigational radioactive agent that targets tumor cells that express SSRT. Nivolumab is an investigational agent that targets and inhibits a pathway that prevents your immune system from effectively fighting your cancer. The combination of these 2 study drugs is investigational. The term "Investigational" in this context means that the drugs have not been approved for clinical use by the US Food and Drug Administration (FDA). Giving Lutathera and nivolumab together may increase the effectiveness of this therapy. We first need to find out the highest dose of Lutathera that can be given safely together with nivolumab. This study will be the first study to test giving Lutathera together with nivolumab. Once we have found the highest dose of Lutathera that can be given with nivolumab, we will treat more patients with this combination to determine how effective it is. The purposes of this study are: To find the highest doses of Lutathera that can be given with nivolumab without causing severe side effects. To find out the side effects seen by giving Lutathera at different dose levels with nivolumab. To determine if the amount of something in your tumor called PD-L1 makes you more likely to have a response to the combination of Lutathera and nivolumab.

Conditions

Small Cell Lung Cancer; Small Cell Lung Cancer Extensive Stage

Keywords

nivolumab; 177Lu-DOTA0-Tyr3-Octreotate; Lutathera

Outcome Measures

Primary Outcomes (2)

• Phase I - Recommended Phase II Dose (RP2D) of 177Lu-DOTA0-Tyr3-Octreotate

  Maximum tolerated dose of 177Lu-DOTA0-Tyr3-Octreotate as determined during the phase I portion.

  12 months

• Phase II - Progression Free Survival

  Time between start of treatment and tumor progression or death

  12 months

Secondary Outcomes (5)

• Number of Participants With Treatment Related Adverse Events

  24 months

• Phase II - Overall Survival

  24 months

• Phase II - Disease Control Rate

  12 months

• Phase II - Objective Response Rate

  12 months

• Phase II - Metabolic Response

  12 months

Study Arms (4)

Phase II - Arm 1

EXPERIMENTAL

Nivolumab will be administered 240mg every 2 weeks. Nivolumab will be given until progressive disease, patient withdrawal, or toxicities. The Phase II dose of 177Lu-DOTA0-Tyr3-Octreotate will be the maximum tolerated dose as determined in the Phase I portion.

Drug: Nivolumab; Radiation: 177Lu-DOTA0-Tyr3-Octreotate

Phase I - Dose Level -1

EXPERIMENTAL

Nivolumab will be administered 240mg every 2 weeks. Nivolumab will be given until progressive disease, patient withdrawal, or toxicities. 177Lu-DOTA0-Tyr3-Octreotate dose will be 3.7 GBq (100 mCi) every 8 weeks for 4 doses.

Drug: Nivolumab; Radiation: 177Lu-DOTA0-Tyr3-Octreotate

Phase I - Dose Level 0

EXPERIMENTAL

Nivolumab will be administered 240mg every 2 weeks. Nivolumab will be given until progressive disease, patient withdrawal, or toxicities. 177Lu-DOTA0-Tyr3-Octreotate dose will be 7.4 GBq (200 mCi) every 8 weeks for 4 doses.

Drug: Nivolumab; Radiation: 177Lu-DOTA0-Tyr3-Octreotate

Phase II - Arm 2

NO INTERVENTION

Patients randomized to this arm will be followed (observation). Cross-over to Phase II Arm 1 at the time of disease progression will be allowed

Interventions

Nivolumab DRUG

Nivolumab is administered intravenously

Also known as: BMS-936558, Opdivo

Phase I - Dose Level -1; Phase I - Dose Level 0; Phase II - Arm 1

177Lu-DOTA0-Tyr3-Octreotate RADIATION

177Lu-DOTA0-Tyr3-Octreotate will be administered every 8 weeks. The first dose of 177Lu-DOTA0-Tyr3-Octreotate will be given two weeks after the first administration of nivolumab. Each dose is infused over 30 minutes. On the day of 177Lu-DOTA0-Tyr3-Octreotate infusion, an intravenous bolus of anti-emetics will be given (suggested options: ondansetron (8 mg), granisetron (3 mg), or tropisetron (5 mg)). Administration of 177Lu-DOTA0-Tyr3-Octreotate may be given one day earlier or delayed up to 1 week due to holidays, inclement weather, conflicts, or similar reasons. Concurrent amino acids are given with each dose of 177Lu-DOTA0-Tyr3-Octreotate since co-infusion of amino acids leads to a significant reduction (47%) in the mean radiation dose to the kidneys. The amino acid solution and 177Lu-DOTA0-Tyr3-Octreotate are administered in parallel by peripheral vein infusion

Also known as: Lutathera

Phase I - Dose Level -1; Phase I - Dose Level 0; Phase II - Arm 1

Eligibility Criteria

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

You may qualify if:

• Phase I
• Patients must have cytologically or histologically confirmed relapsed or refractory extensive-disease small-cell lung cancer (ES-SCLC) or non-progressing ES-SCLC after first line chemotherapy, or advanced or inoperable grade I-II pulmonary NETs.
• Patients with tumor tissue uptake during NETSPOT® PET that is equal to or higher than that in normal hepatic tissue (grade ≥2) will be eligible. At the discretion of the principal investigator, patients with SCLC whose tumors have lower levels of uptake than liver during NETSPOT® PET may be eligible for the study.
• Patients must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan. See Section 7.1.2 for the evaluation of measurable disease.
• Toxicities of prior therapy must be resolved to grade 1 or less as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
• Prior radiotherapy or radiosurgery (including prophylactic cranial radiation and/or thoracic radiation) must have been completed at least 2 weeks prior to randomization.
• ECOG performance status of 0-1.
• Adequate organ and bone marrow function (hemoglobin \> 9 g/dL; absolute neutrophil count \> 1.5 x 109/L; platelet counts \> 100 x 109/L; serum bilirubin \< 2 x ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 x ULN or \< 5 x ULN if liver metastases; calculated creatinine clearance \> 50 mL/min).
• Life expectancy of at least 3 months.
• Age \> 18 years.
• Women of childbearing potential (WOCBP) must use avoid pregnancy for 23 weeks after the last dose of investigational drug. Men who are sexually active with WOCBP must avoid pregnancy for 31 weeks after the last dose of investigational drug. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) are not required to avoid pregnancy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropic \[HCG\]) within 24 hours prior to the start of the study drug.
• Women must not be pregnant or breastfeeding.
• Ability to understand and willingness to sign a written informed consent document.
• Phase II

You may not qualify if:

• Phase I
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
• Patients with human immunodeficiency virus (HIV) infection, or active hepatitis B or C virus infection will be excluded.
• Patients who received prior anti-tumoral radionuclide therapy (with unsealed sources) are not eligible for the study.
• Prior major surgery within 12 weeks or prior major surgery from which the patient has not sufficiently recovered yet.
• Untreated and uncontrolled second tumor in the past 2 years.
• Logistical or psychological hindrance to participation in clinical research.
• Uncontrolled or significant cardiovascular disease, including any of the following:
• Symptomatic congestive heart failure (New York Heart Association Classification Class II).
• Cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), or unstable angina.
• Uncontrolled hypertension or uncontrolled cardiac arrhythmia.
• Any other medical condition that in the Investigator's opinion would not make the patient a good candidate for the study.
• Phase II

Sponsors & Collaborators

• Georgetown University: lead
• Bristol-Myers Squibb: collaborator
• Advanced Accelerator Applications: collaborator

Study Sites (2)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (1)

• Kim C, Liu SV, Subramaniam DS, Torres T, Loda M, Esposito G, Giaccone G. Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung. J Immunother Cancer. 2020 Jul;8(2):e000980. doi: 10.1136/jitc-2020-000980.

  PMID: 32616557 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Nivolumab; lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chul Kim, MD
• Organization: Georgetown University

Chul.Kim@gunet.georgetown.edu

202-444-2223

Study Officials

• Chul Kim, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: October 26, 2017
• First Posted: October 30, 2017
• Study Start: November 20, 2017
• Primary Completion: March 28, 2019
• Study Completion: August 11, 2020
• Last Updated: March 16, 2021
• Results First Posted: March 16, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)