Carcinoma, Non-Small-Cell LungPhase 1/2NCT03663166
Radiation and Chemotherapy With Ipilimumab Followed by Nivolumab for Patients With Stage III Unresectable Non-Small Cell Lung Cancer (NSCLC)
A Phase 1/2 study testing Thoracic Radiotherapy, Platinum Based Chemotherapy and ipilimumab in people with Carcinoma, Non-Small-Cell Lung, run by H. Lee Moffitt Cancer Center and Research Institute at 3 sites in United States.
Trial summary
This study is to determine if Stage III NSCLC patients treated with ipilimumab with thoracic radiation therapy followed by nivolumab monotherapy every 4 weeks for up to 12 months show an improved 12-month Progression Free Survival (PFS) rate compared with a 12-month historical PFS rate of 49% among patients treated in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Thoracic Radiotherapy, Platinum Based Chemotherapy and ipilimumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 3 sitesUnited States
- Study dates
- 20 Nov 2018to 22 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Over 18 years of age
- Participants must have signed and dated a written informed consent form.
- Participants must be willing and able to comply with proposed visit and treatment schedule.
- Patients with NSCLC documented by histology or cytology from brushing, washing, or needle aspiration of a defined lesion, but not from sputum cytology alone.
- Patients must have presented at initial diagnosis with Stage III disease according to American Joint Committee on Cancer (AJCC) Staging Manual, 8th Edition;
- Patients must be deemed by the treating investigator to be surgically unresectable. I
Show all 15Show fewer
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
- Patients must initiate study treatment 60 days from the date of pathologic diagnosis.
- Tumor biopsy specimen including at least formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or 10 unstained slides of tumor sample (archival or recent) for biomarker evaluation must be available for submission to the central lab for correlative studies.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 14 days prior to the start of thoracic radiation therapy.
- Male participants must be willing to refrain from sperm donation during the entire study and for 5 half-lives of study drug plus 90 days (duration of sperm turnover).
- Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception which have a failure rate of </= 1% when used consistently and correctly. Azoospermic males are exempt from contraceptive requirements.
- 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.
- WOCBP who are continuously not heterosexually active are exempt from contraception requirements. However, they must still undergo pregnancy testing as described in this section.
- 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
Who cannot join
- 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). Exceptions may apply.
- 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 study initiation. 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
- Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
Show all 16Show fewer
- Any patient requiring supplemental oxygen therapy.
- Previous malignancies (except non-melanoma skin cancers, and some in situ cancers) 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.
- Inadequate hepatic function.
- Inadequate pancreatic function.
- History of allergy or hypersensitivity to any of the study drugs or study drug components
Trial locations and contacts
3 sites in 1 country.
United States3 sites
UNC Limeberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Duke University
Durham, North Carolina, 27710
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: Radiation and Chemotherapy With Ipilimumab Followed by Nivolumab for Patients With Stage III Unresectable NSCLC
This study is to determine if Stage III NSCLC patients treated with ipilimumab with thoracic radiation therapy followed by nivolumab monotherapy every 4 weeks for up to 12 months show an improved 12-month Progression Free Survival (PFS) rate compared with a 12-month historical PFS rate of 49% among patients treated in a similar fashion with concurrent chemoradiotherapy.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Thoracic Radiotherapy, Platinum Based Chemotherapy, ipilimumab, Nivolumab
- Keywords
- Lung, Unresectable NSCLC, Radiation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thoracic RadiotherapyRadiation
2 Gy in 30 fractions directed at all sites of suspected disease
Platinum Based ChemotherapyDrug
Platinum based chemotherapy including cisplatin and etoposide, carboplatin and paclitaxel or cisplatin and pemetrexed (for patients with non-squamous histology).
ipilimumabDrug
ipilimumab 1mg/kg delivered concurrently with initiation of chemoradiotherapy and in week 4 of chemoradiotherapy
NivolumabDrug
Nivolumab 480 mg (30 minute IV infusion) at least 7 days but no more than 21 days after completion of radiation and chemotherapy every 4 weeks for up to 12 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Radiation and Chemotherapy | Experimental | Thoracic Radiotherapy with cytotoxic platinum based chemotherapy with cytotoxic platinum based chemotherapy including cisplatin and etoposide, carboplatin and paclitaxel or cisplatin and pemetrexed (for patients with non-squamous histology) and Ipilimumab. Receives: Radiation: Thoracic Radiotherapy; Drug: Platinum Based Chemotherapy; Drug: ipilimumab |
| Nivolumab | Experimental | Nivolumab 480 mg (30 minute IV infusion) after completion of radiation and chemotherapy for up to 12 cycles until progression. Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unacceptable Toxicity Status at the End of 8-week Safety Observation Period
Unacceptable toxicity defined as:
- Any grade 4 immune related adverse event (irAE)
- Any grade 3 irAE, excluding pneumonitis, that does not downgrade to grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to ≤ grade 1 or baseline within 14 days
- Liver transaminase elevation > 8 × ULN or total bilirubin > 5 × ULN,
- Any ≥ grade 3 non-irAE, with some exclusions. Result is provided as number of participants with unacceptable toxicity within 8 weeks of commencing study therapy.
Measured: At 8 weeks of treatment
Percentage of Participants Without Disease Progression at 12 Months
Disease Progression defined as the duration from date of registration to date of first documentation of progression as defined using Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and assessed by local investigator or symptomatic deterioration (as defined in Outcome 1) or death due to any cause. Patients last known to be alive without report of progression are censored at date of last disease assessment. For patients with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan (as defined by the disease assessment schedule) will be used as the date of progression.
Measured: 12 months post treatment
Secondary outcomes (2)
Percentage of Participants Who Experienced 12 Month Distant Metastasis Free Survival (DMFS)
DMFS is defined as the duration from date of registration to date of first documentation of distant metastatic progression beyond the primary tumor site as well as regional lymph nodes assessed by local investigator or symptomatic deterioration (as defined in Outcome 1) or death due to any cause. Patients last known to be alive without report of distant metastatic progression are censored at date of last disease assessment.
Measured: 12 months post treatment
Objective Response Rate (ORR) at 6 Months
ORR is defined as the proportion of all treated subjects whose best overall response is either a complete response or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Best Objective Response (BOR) will also be reported Complete Response (CR) or Partial Response (PR) determinations included in the assessment must be confirmed by a consecutive second (confirmatory) evaluation meeting the criteria for response that is performed at least 4 weeks after the criteria for response are first met. When Stable Disease (SD) is believed to be the best response, it must meet a minimum SD duration of 49 days. Measurements must have met the SD criteria at least once after study entry.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2018
- Study start20 Nov 2018
- Primary completion22 Oct 2021
- Study completion22 Oct 2021
Why it stopped: Increased SAE occurrence per PI
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bradford Perez, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03663166
- Sponsor's protocol ID
- MCC-19704
- Status last verified
- Feb 2023
- First submitted
- 6 Sep 2018
- Last updated
- 15 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiation and Chemotherapy With Ipilimumab Followed by Nivolumab for Patients With Stage III Unresectable NSCLC
- ClinicalTrials.gov ID
- NCT03663166
- Acronym / sponsor ID
- MCC-19704
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- Lung, Unresectable NSCLC, Radiation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Increased SAE occurrence per PI
- Enrolment
- 19 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Study start
- 20 Nov 2018 (actual)
- Primary completion
- 22 Oct 2021 (actual)
- Study completion
- 22 Oct 2021 (actual)
- First posted
- 10 Sep 2018 (actual)
- Results
- Posted 15 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to determine if Stage III NSCLC patients treated with ipilimumab with thoracic radiation therapy followed by nivolumab monotherapy every 4 weeks for up to 12 months show an improved 12-month Progression Free Survival (PFS) rate compared with a 12-month historical PFS rate of 49% among patients treated in a similar fashion with concurrent chemoradiotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiation and Chemotherapy | Experimental | Radiation: Thoracic Radiotherapy, Drug: Platinum Based Chemotherapy, Drug: ipilimumabThoracic Radiotherapy with cytotoxic platinum based chemotherapy with cytotoxic platinum based chemotherapy including cisplatin and etoposide, carboplatin and paclitaxel or cisplatin and pemetrexed (for patients with non-squamous histology) and Ipilimumab. |
| Nivolumab | Experimental | Drug: NivolumabNivolumab 480 mg (30 minute IV infusion) after completion of radiation and chemotherapy for up to 12 cycles until progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Over 18 years of age
- Participants must have signed and dated a written informed consent form.
- Participants must be willing and able to comply with proposed visit and treatment schedule.
- Patients with NSCLC documented by histology or cytology from brushing, washing, or needle aspiration of a defined lesion, but not from sputum cytology alone.
- Patients must have presented at initial diagnosis with Stage III disease according to American Joint Committee on Cancer (AJCC) Staging Manual, 8th Edition;
Key exclusion criteria (16 listed)
- 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). Exceptions may apply.
- 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 study initiation. 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thoracic Radiotherapy2 Gy in 30 fractions directed at all sites of suspected disease | Radiation | Radiation and Chemotherapy |
| Platinum Based ChemotherapyPlatinum based chemotherapy including cisplatin and etoposide, carboplatin and paclitaxel or cisplatin and pemetrexed (for patients with non-squamous histology). | Drug | Radiation and Chemotherapy |
| ipilimumabipilimumab 1mg/kg delivered concurrently with initiation of chemoradiotherapy and in week 4 of chemoradiotherapy | Drug | Radiation and Chemotherapy |
| NivolumabNivolumab 480 mg (30 minute IV infusion) at least 7 days but no more than 21 days after completion of radiation and chemotherapy every 4 weeks for up to 12 cycles. | Drug | Nivolumab |
Primary outcome
Unacceptable Toxicity Status at the End of 8-week Safety Observation Period
Time frame: At 8 weeks of treatment
Unacceptable toxicity defined as: * Any grade 4 immune related adverse event (irAE) * Any grade 3 irAE, excluding pneumonitis, that does not downgrade to grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to ≤ grade 1 or baseline within 14 days * Liver transaminase elevation > 8 × ULN or total bilirubin > 5 × ULN, * Any ≥ grade 3 non-irAE, with some exclusions. Result is provided as number of participants with unacceptable toxicity within 8 weeks of commencing study therapy.
Percentage of Participants Without Disease Progression at 12 Months
Time frame: 12 months post treatment
Disease Progression defined as the duration from date of registration to date of first documentation of progression as defined using Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and assessed by local investigator or symptomatic deterioration (as defined in Outcome 1) or death due to any cause. Patients last known to be alive without report of progression are censored at date of last disease assessment. For patients with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan (as defined by the disease assessment schedule) will be used as the date of progression.
2 secondary outcomes
Percentage of Participants Who Experienced 12 Month Distant Metastasis Free Survival (DMFS)
Time frame: 12 months post treatment
Objective Response Rate (ORR) at 6 Months
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Moffitt Cancer Center Clinical Trials WebsiteLink provided by the sponsor.
Related trials for Carcinoma, Non-Small-Cell Lung
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bradford Perez, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Thoracic Radiotherapy, Platinum Based Chemotherapy and ipilimumab in people with Carcinoma, Non-Small-Cell Lung, run by H. Lee Moffitt Cancer Center and Research Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unacceptable Toxicity Status at the End of 8-week Safety Observation Period (time frame: At 8 weeks of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2023.