Ipilimumab + Nivolumab w/Thoracic Radiotherapy for Extensive-Stage Small Cell Lung Cancer

NCT ID: NCT03043599

Last Updated: 2024-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-13
• Study Completion Date: 2023-11-16

Brief Summary

The purpose of the safety run in Phase I portion of this study is to confirm the recommended Phase II dose of ipilimumab and nivolumab among participants treated with combined thoracic radiation therapy (30 Gy in 10 fractions) and nivolumab/ipilimumab following standard treatment with 4-6 cycles of platinum-based chemotherapy.

The purpose of the Phase II portion of this study is to estimate the 6-month Progression Free Survival (PFS) rate among participants treated with ipilimumab and nivolumab with thoracic radiation therapy (30 Gy in 10 fractions) after standard treatment with 4 to 6 cycles of platinum based chemotherapy.

Detailed Description

This study is a nonrandomized, phase II, single arm, multicenter trial evaluating safety and efficacy of thoracic radiation therapy followed by nivolumab and ipilimumab in participants with Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) who have completed a first-line platinum-based chemotherapy regimen and achieved ongoing complete response (CR), partial response (PR), or stable disease (SD). This study will determine whether nivolumab and ipilimumab delivered 2 weeks following consolidative thoracic radiation therapy demonstrates acceptable toxicity and whether the treatment regimen will improve 6-month progression-free survival (PFS) compared with a similar historical control cohort in this participant population. Additional objectives include further characterization of overall survival, adverse event profile, patterns of failure analysis, and potential predictive biomarkers of response to nivolumab in combination with ipilimumab and thoracic radiation therapy in patients with ED-SCLC.

Conditions

Small Cell Lung Cancer; Extensive-stage Small Cell Lung Cancer

Keywords

Thoracic; Radiotherapy; Platinum Based Chemotherapy; Immunotherapy; Ipilimumab; Nivolumab; Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination Therapy

Consolidative Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Based Chemotherapy. Radiotherapy, followed by a 14 to 21 day break between radiotherapy and the beginning of study drug treatment.

Group Type: EXPERIMENTAL

Thoracic Radiation Therapy

Intervention Type: RADIATION

All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).

Ipilimumab

Intervention Type: DRUG

Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.

Nivolumab

Intervention Type: DRUG

Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.

Interventions

Thoracic Radiation Therapy

All participants will receive radiation therapy (3Gy x 10 fractions) to the chest for 10 days (Monday through Friday for 2 weeks).

Intervention Type: RADIATION

Ipilimumab

Ipilimumab 3 mg/kg (90 minute IV infusion) will be administered every 3 weeks for 4 doses.

Intervention Type: DRUG

Nivolumab

Nivolumab 1 mg/kg (30 minute IV infusion) will be administered every 3 weeks for 4 doses, followed by nivolumab 480 mg every 4 weeks.

Intervention Type: DRUG

Other Intervention Names

radiotherapy; YERVOY; OPDIVO

Eligibility Criteria

Inclusion Criteria

• Signed Written Informed Consent
• Willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
• Patients with Small Cell Lung Cancer (SCLC) documented by histology or cytology from brushing, washing, or needle aspiration of a defined lesion, but not from sputum cytology alone
• Have presented at initial diagnosis with extensive-stage disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
• Have received 4-6 cycles of platinum-based first-line chemotherapy and have an ongoing response of complete response (CR), partial response (PR), or stable disease (SD) after completion of chemotherapy. Acceptable combinations, as recommended per National Comprehensive Cancer Network (NCCN) guidelines, include cisplatin or carboplatin combined with either etoposide or irinotecan; As an exception to the above criterion, participants receiving only 3 cycles of chemotherapy due to toxicity are eligible, if they have an ongoing PR or CR after the 3rd cycle; Participants who have received > 6 cycles of platinum-based first-line chemotherapy are not eligible.
• Participants must initiate study treatment with thoracic radiation therapy less than or equal to 8 weeks (56 days) from the last dose of platinum-based first line chemotherapy.
• Whenever possible, a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or 10 unstained slides of tumor sample (archival or recent) for biomarker evaluation should be made available and submitted to the central lab for correlative studies.
• Participant re-enrollment: This study permits the re-enrollment of a participant who has discontinued the study due to pre-treatment failure (i.e., participant has not been treated). If re-enrolled, the participant must be re-consented.
• Men and women at least 18 years of age
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of thoracic radiation therapy
• Women must not be breastfeeding.
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug (half-life up to 25 days) plus 30 days (duration of ovulatory cycle) for a total of 5 months post-treatment completion.
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of the study drug (half-life up to 25 days) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion.
• Additional criteria may apply

Exclusion Criteria

• Participants with previous brain metastases are eligible provided that they are treated and asymptomatic not requiring steroids or anticonvulsants, and have stable disease at the screening tumor assessment. A 4 week disease stable interval as confirmed by MRI or CT brain with contrast is required after treatment of brain metastases before initiation of thoracic radiation therapy. In addition, participants must have been either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent).
• Participants who have received prior chest radiation which at the discretion of the treating radiation oncologist precludes delivery of protocol radiation therapy
• Carcinomatous meningitis
• Pleural effusion that cannot be controlled with appropriate interventions
• All toxicities attributed to prior anti-cancer therapy must have been resolved to Grade 1 (NCI CTCAE Version 4) or baseline before administration of study drug(s) other than: Patients with toxicities attributed to prior anti-cancer therapy that either are not expected to resolve and/or result in long-lasting sequelae, such as neuropathy after platinum-based therapy, or are not expected to interfere with treatment on study, such as fatigue,alopecia, or grade 2 hematologic toxicity are eligible.
• Women who are pregnant or breastfeeding
• Active, known, or suspected autoimmune disease. Patients with an autoimmune paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Corticosteroids with minimal systemic absorption (inhaled or topical steroids) and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways)
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• Any patient requiring supplemental oxygen therapy
• Previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
• Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug(s) administration or interfere with the interpretation of safety results
• Major surgery or significant traumatic injury that is not recovered at least 14 days before the initiation of thoracic radiation therapy.
• Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection
• Individuals with a positive test for HCV antibody but no detection of HCV RNA indicating no current infection are eligible
• Known medical history of testing positive for human immunodeficiency virus (HIV) or known medical history of acquired immunodeficiency syndrome (AIDS)
• Inadequate hematologic function according to study guidelines
• Inadequate hepatic function according to study guidelines
• History of allergy or hypersensitivity to any of the study drugs or study drug components
• Additional criteria may apply

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bradford A. Perez, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

References

Perez BA, Kim S, Wang M, Karimi AM, Powell C, Li J, Dilling TJ, Chiappori A, Latifi K, Rose T, Lannon A, MacMillan G, Saller J, Grass GD, Rosenberg S, Gray J, Haura E, Creelan B, Tanvetyanon T, Saltos A, Shafique M, Boyle TA, Schell MJ, Conejo-Garcia JR, Antonia SJ. Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2021 Feb 1;109(2):425-435. doi: 10.1016/j.ijrobp.2020.09.031. Epub 2020 Sep 28.

Reference Type: DERIVED

PMID: 33002543 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CA209-840

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-18914

Identifier Type: -

Identifier Source: org_study_id