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Stage I Lung Non-Small Cell Cancer AJCC v7Phase 2NCT03158129

Nivolumab With or Without Ipilimumab or Chemotherapy in Treating Patients With Previously Untreated Stage I-IIIA Non-small Cell Lung Cancer

A Phase 2 study testing Carboplatin, Cisplatin and Docetaxel in people with Stage I Lung Non-Small Cell Cancer AJCC v7 and Stage IA Lung Non-Small Cell Carcinoma AJCC v7, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well nivolumab works when given alone and in combination with ipilimumab or chemotherapy in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, Cisplatin and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
1 siteUnited States
Study dates
16 Jun 2017to 13 Nov 2024
Phase
Phase 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

  • Histologically or cytologically confirmed previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study. Neuroendocrine carcinomas are not eligible. Carcinomas with neuroendocrine differentiation are eligible
  • Patients with stage IA or stage IB < 4 cm (according to American Joint Committee on Cancer [AJCC] 7th edition) are eligible for randomization into arms A and B only. Patients with stage IB >= 4 cm, IIA, IIB, or IIIA disease (according to AJCC 7th edition) are eligible for randomization into arms A, and B, and for enrollment into arms C and D
  • Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor
  • All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease
  • The patient must be a suitable candidate for surgery, in the opinion of the treating physician
  • Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation
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  • Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Hemoglobin >= 8.0 g/dL
  • Platelets >= 100 x 10^9/L
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin < 3.0 mg/dL)
  • Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance >= 50 mL/min

Who cannot join

  • Prior systemic therapy or radiation therapy for treatment of the current lung cancer
  • Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug
  • Pregnant or lactating female: Women of childbearing potential (WOCB) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the start of nivolumab; Women of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
  • Unwillingness or inability to follow the procedures required in the protocol
  • Patients with pre-existing sensorineural hearing impairment/loss or newly diagnosed as documented by an audiology assessment performed prior to study enrollment may not be eligible for cisplatin and may be dispositioned to carboplatin, as determined by the treating physician.
  • Patients with a history of severe hypersensitivity reaction to taxotere and or polysorbate 80 must be excluded
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  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
  • 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. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted
  • Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
  • Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid indicating acute or chronic infection
  • Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome
  • History of severe hypersensitivity reaction to any monoclonal antibody and/or to study drug components
  • Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
  • Patients who are sexually active, with preserved reproductive capacity, and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during and after the trial
  • Women of child bearing potential (WOCBP) should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug(s); Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; Women who are not of childbearing potential as well as azoospermic men do not require contraception
  • Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase II Study of Induction Checkpoint Blockade for Untreated Stage I-IIIA Non-Small Cell Lung Cancers Amenable for Surgical Resection

This phase II trial studies how well nivolumab works when given alone and in combination with ipilimumab or chemotherapy in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin, docetaxel, and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab with ipilimumab or chemotherapy may work better in treating patients with non-small cell lung cancer compared to chemotherapy alone.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the major pathologic response rate (MPRR) in patients treated with induction nivolumab, nivolumab plus ipilimumab, and nivolumab plus platinum-based chemotherapy.

SECONDARY OBJECTIVES:

  1. Toxicity (assessed by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4).

II. Peri-operative morbidity and mortality. III. CD8 positive (+) tumor infiltrating lymphocytes (TILs) in resected tumor tissues of patients treated with nivolumab alone and nivolumab plus ipilimumab and nivolumab plus platinum-based chemotherapy.

IV. Quantification of CD8+ TILs will be assessed by counting the cells positive for staining with an anti-CD8 antibody by immunohistochemistry in five random square areas (1 mm^2 each) in both intratumoral and peritumoral compartments using the automated Aperio system.

  1. Response rates to induction treatment (by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1).

VI. Recurrence-free survival. VII. Overall survival. VIII. To correlate major pathologic response with recurrence-free and overall survival.

IX. Complete resection (R0) rate. X. Pathologic complete response (pCR) in resected tumor specimens. XI. To correlate response assessed by imaging studies with outcomes (both major pathologic response to treatment and long-term recurrence-free survival).

XII. To correlate blood, tissue, and stool-based biomarkers with efficacy and toxicity.

EXPLORATORY OBJECTIVES:

  1. To identify novel prognostic and predictive markers present at diagnosis. II. To determine modulation of markers by induction immunotherapy and/or immunotherapy plus platinum-based chemotherapy in order to inform future translational studies.

OUTLINE: Patients are randomized to Arms A and B and enrolled in Arm C or D after completion of enrollment to Arms A and B.

ARM A: Patients receive nivolumab intravenously (IV) over 60 minutes on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive nivolumab as in Arm A and receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive nivolumab IV over 30 minutes and cisplatin IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

ARM D: Patients receive ipilimumab IV over 90 minutes on day 1, nivolumab IV over 30 minutes on days 1, 22, and 43, and cisplatin (or carboplatin) IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment and surgery, patients are followed up at 8 weeks.

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.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • DocetaxelDrug

    Also called Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

    Given IV

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010

    Given IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • PemetrexedDrug

    Also called MTA, Multitargeted Antifolate, Pemfexy

    Given IV

Study groups in NCT03158129
Study groupRoleWhat they receive
Arm A (nivolumab)ExperimentalParticipants receive nivolumab IV over 60 minutes on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Nivolumab
Arm B (nivolumab, ipilimumab)ExperimentalParticipants receive nivolumab as in Arm A and receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Ipilimumab; Biological: Nivolumab
Arm C (nivolumab, cisplatin, docetaxel, pemetrexed)ExperimentalPatients receive nivolumab IV over 30 minutes and cisplatin IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cisplatin; Drug: Docetaxel; Biological: Nivolumab; Drug: Pemetrexed
Arm D (ipilimumab, nivolumab, chemotherapy)ExperimentalPatients receive ipilimumab IV over 90 minutes on day 1, nivolumab IV over 30 minutes on days 1, 22, and 43, and cisplatin (or carboplatin) IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carboplatin; Drug: Cisplatin; Drug: Docetaxel; Biological: Ipilimumab; Biological: Nivolumab; Drug: Pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major Pathologic Response (mPR)

    The percentage of viable tumor cells was averaged across all reviewed tumor slides from the lung resection specimen. The specimen was reviewed by two pathologists and average score was used. Tumors with ≤ 10% of viable tumor cells were considered to have undergone MPR. Patients who did not have surgery was considered to be no MPR.

    Measured: The lung resection specimen was collected at surgery.

Secondary outcomes (7)

  1. Pathologic Complete Response (pCR)

    The percentage of viable tumor cells was averaged across all reviewed tumor slides from the lung resection specimen. The specimen was reviewed by two pathologists and average score was used. Tumors with 0% of viable tumor cells were considered to have undergone pCR. Patients who did not have surgery was considered to be no pCR.

    Measured: The lung resection specimen was collected at surgery.

  2. Radiographic Response

    Radiographic response to induction treatment was assessed by RECIST version 1.1

    Measured: Reassessment after induction therapy

  3. Overall Survival (OS)

    Overall survival was defined as the time from randomization (in Arm A and Arm B) or treatment initiation (in Arm C and Arm D) to the time of death from all causes or to the time of last follow-up.

    Measured: In Arms A and B, the cutoff date was 2020-2-25. The median follow-up time frame was 22.2 months. In Arms C and D, the cutoff date was 2022-7-18. The median follow-up time frames were 39.2 and 24.0 months respectively

  4. Event-free Survival (EFS)

    EFS was defined as the time from randomization (in Arm A and Arm B) or treatment initiation (in Arm C and Arm D) to any progression of primary lung cancer precluding planned surgery, any progression or recurrence (as assessed by imaging and/or histopathologically) of primary lung cancer after surgery, any progression of primary lung cancer in patients without surgery or death from all causes or to the time of last imaging.

    Measured: In Arms A and B, the cutoff date was 2020-2-25. The median follow-up time frame was 22.2 months. In Arms C and D, the cutoff date was 2022-7-18. The median follow-up time frames were 39.2 and 24.0 months respectively.

  5. Residual Tumor Classification

    The residual tumor (R) classification measures how well the lung tumor was removed by surgery in the anatomic extent. R0 means a complete resection. R1 means a macroscopically complete resection but with microscopic tumor at the surgical margin. R2 means a resection that leaves gross tumor behind. R0 resection is a better surgical outcome than R1, R2 resections and R2 is the worst surgical outcome. The number of R0, R1 and R2 resections were reported among the patients who underwent surgery.

    Measured: At surgery

  6. 30-day Postoperative Complication

    The number of patients who had complications including pulmonary, cardiac, gastrointestinal, genitourinary, neurological, and wound within 30 days after surgery

    Measured: Within 30 days after surgery

  7. 90-day Mortality

    The number of patients who died within 90 days after surgery

    Measured: Within 90 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2017
  2. Study start16 Jun 2017
  3. Primary completion13 Nov 2024
  4. Study completion13 Nov 2024

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03158129
Sponsor's protocol ID
2016-0982
Other IDs
NCI-2018-01210, 2016-0982
Status last verified
Mar 2026
First submitted
16 May 2017
Last updated
6 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Cascone T, Leung CH, Weissferdt A, Pataer A, Carter BW, Godoy MCB, Feldman H, William WN Jr, Xi Y, Basu S, Sun JJ, Yadav SS, Rojas Alvarez FR, Lee Y, Mishra AK, Chen L, Pradhan M, Guo H, Sinjab A, Zhou N, Negrao MV, Le X, Gay CM, Tsao AS, Byers LA, Altan M, Glisson BS, Fossella FV, Elamin YY, Blumenschein G Jr, Zhang J, Skoulidis F, Wu J, Mehran RJ, Rice DC, Walsh GL, Hofstetter WL, Rajaram R, Antonoff MB, Fujimoto J, Solis LM, Parra ER, Haymaker C, Wistuba II, Swisher SG, Vaporciyan AA, Lin HY, Wang J, Gibbons DL, Jack Lee J, Ajami NJ, Wargo JA, Allison JP, Sharma P, Kadara H, Heymach JV, Sepesi B. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial. Nat Med. 2023 Mar;29(3):593-604. doi: 10.1038/s41591-022-02189-0. Epub 2023 Mar 16.

    PubMed 36928818

  • Cascone T, Weissferdt A, Godoy MCB, William WN Jr, Leung CH, Lin HY, Basu S, Yadav SS, Pataer A, Mitchell KG, Khan MAW, Shi Y, Haymaker C, Solis LM, Parra ER, Kadara H, Wistuba II, Sharma P, Allison JP, Ajami NJ, Wargo JA, Jenq RR, Gibbons DL, Lee JJ, Swisher SG, Vaporciyan AA, Heymach JV, Sepesi B. Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer. Nat Commun. 2021 Aug 19;12(1):5045. doi: 10.1038/s41467-021-25188-0.

    PubMed 34413300

  • Cascone T, William WN Jr, Weissferdt A, Leung CH, Lin HY, Pataer A, Godoy MCB, Carter BW, Federico L, Reuben A, Khan MAW, Dejima H, Francisco-Cruz A, Parra ER, Solis LM, Fujimoto J, Tran HT, Kalhor N, Fossella FV, Mott FE, Tsao AS, Blumenschein G Jr, Le X, Zhang J, Skoulidis F, Kurie JM, Altan M, Lu C, Glisson BS, Byers LA, Elamin YY, Mehran RJ, Rice DC, Walsh GL, Hofstetter WL, Roth JA, Antonoff MB, Kadara H, Haymaker C, Bernatchez C, Ajami NJ, Jenq RR, Sharma P, Allison JP, Futreal A, Wargo JA, Wistuba II, Swisher SG, Lee JJ, Gibbons DL, Vaporciyan AA, Heymach JV, Sepesi B. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat Med. 2021 Mar;27(3):504-514. doi: 10.1038/s41591-020-01224-2. Epub 2021 Feb 18.

    PubMed 33603241

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Cisplatin and Docetaxel in people with Stage I Lung Non-Small Cell Cancer AJCC v7 and Stage IA Lung Non-Small Cell Carcinoma AJCC v7, run by M.D. Anderson Cancer Center at 1 site 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 12 inclusion and 17 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: finished, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 phase mean?

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 5 Mar 2025). 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?

Major Pathologic Response (mPR) (time frame: The lung resection specimen was collected at surgery.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03158129, which also lists 3 linked publications.

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 6 Apr 2026.

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