Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer

NCT03728361 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-18184NCI-2018-02050
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well nivolumab and temozolomide work in treating patients with small-cell lung cancer that has come back or does not respond to treatment, or neuroendocrine cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as temozolomide, 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 and temozolomide may work better in treating patients with small-cell lung cancer and neuroendocrine cancer.

Conditions

Grade I Neuroendocrine Carcinoma; Grade II Neuroendocrine Carcinoma; Grade III Neuroendocrine Carcinoma; Metastatic Neuroendocrine Carcinoma; Neuroendocrine Carcinoma; Recurrent Small Cell Lung Carcinoma; Refractory Small Cell Lung Carcinoma; Lung Cancer Stage IV; Large Cell Neuroendocrine Carcinoma; Neuroendocrine Tumors; Small Cell Lung Cancer Metastatic; Small-cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

  Response will be defined by a complete response (CR) or partial response (PR), confirmed or unconfirmed. Response will be defined for patients with measurable disease and who receive at least one dose of combination treatment. Exact binomial 95% confidence intervals for the true PR+CR response rate will be calculated.

  Up to 3 years

Secondary Outcomes (4)

• Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  Up to 3 years

• Progression-free survival (PFS)

  The time from allocation to the first documented disease progression according to RECIST 1.1 or death due to any cause, whichever occurs first, assessed up to 3 years

• Central nervous system (CNS) PFS

  The time from allocation to the first documented disease progression within the CNS according to RECIST 1.1, assessed up to 3 years

• Overall survival (OS) of patients

  Up to 3 years

Other Outcomes (1)

• Exploratory Biomarker analysis

  Up to 3 years

Study Arms (1)

Treatment (nivolumab, temozolomide)

EXPERIMENTAL

Patients receive nivolumab IV on day 1 of a 28 day cycle. Patients also receive temozolomide PO on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab; Drug: Temozolomide

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nivolumab, temozolomide)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac

Treatment (nivolumab, temozolomide)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial
• For Cohort 1: Have histologically or cytologically-documented diagnosis of advanced (metastatic and/or unresectable) small cell lung cancer and have progressed or recurred after platinum-based chemotherapy with immunotherapy. Eligible patients will be defined as follows:
• Sensitive disease: Patients who had one previous line of chemotherapy and relapsed after \> 90 days of completion of treatment
• Refractory disease: Patients with no response to first-line chemotherapy or progression \< 90 days after completing treatment.
• For cohort 1: maximum of 2 prior lines of therapy is allowed (ie second or third line treatment)
• For Cohort 2: Have histologically or cytologically-documented diagnosis of advanced (metastatic and/or unresectable) neuroendocrine tumor/carcinoma of any grade (World Health Organization \[WHO\] Grade 1-3) of any origin, in any line of therapy (ie both treatment na?ve and pre-treated patients allowed), and have clinical or biochemical or radiographic progression in the 12 months prior to study registration. Concomitant use of a somatostatin analogue is allowed, as long as patients have been on a stable dose for at least 2 months
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• For Cohort 1: Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block. A recently obtained archival FFPE tumor tissue block from a primary or metastatic tumor resection or biopsy can be provided if it was obtained within 1 year of trial screening. Patients with tumor specimens older than 1 year may still be eligible if deemed so by study sponsor. For Cohort 2: archival tissue as above is preferred, but not required for trial entry. Verification of tumor burden in the biopsy is encouraged. For optimal biomarker results, tumor content should be \> 30% of total tissue area
• Be willing to provide peripheral blood samples at screening and day 1 of cycles 1, 2 and 3 as well as at progressive disease for correlative studies
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Life expectancy greater than 3 months
• Ability to swallow and retain oral medication
• Absolute neutrophil count (ANC) \>= 1,500 /mcL (performed within 28 days of treatment initiation)
• Platelets \>= 100,000 / mcL (performed within 28 days of treatment initiation)
• Serum creatinine =\< 2.0 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl) \>= 50 mL/min as estimated by Cockcroft and Gault formula for subject with creatinine levels \> 2 X institutional ULN (performed within 28 days of treatment initiation)

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has received prior temozolomide therapy
• Prior immunotherapy with checkpoint inhibitors (including antibodies to PD-1, PD-L1, is allowed only in Cohort 1 and must have been given in combination with chemotherapy as part of first line treatment. Prior CTLA-4 therapy is excluded in both cohorts.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to nivolumab or temozolomide or any of their excipients
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: Subjects with =\< grade 2 neuropathy due to chemotherapy are an exception to this criterion and may qualify for the study
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment
• Has symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with asymptomatic lesions will be eligible if considered appropriate by the treating physician. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not requiring steroids (or are on a stable or decreasing dose of steroids equivalent to 10 mg prednisone or less) for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has active autoimmune disease, including myasthenic syndrome, which has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Sponsors & Collaborators

• Dwight Owen: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Ohio State University Comprehensive Cancer Center-COHORT 1

Columbus, Ohio, 43210, United States

Location

Ohio State University Comprehensive Cancer Center-COHORT 2

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Owen DH, Benner B, Pilcher C, Good L, Savardekar H, Norman R, Ghattas C, Shah M, Konda B, Verschraegen CF, Wesolowski R, Behbehani GK, Carson WE, Otterson GA. Deep and Durable Response to Nivolumab and Temozolomide in Small-Cell Lung Cancer Associated With an Early Decrease in Myeloid-Derived Suppressor Cells. Clin Lung Cancer. 2021 Jul;22(4):e487-e497. doi: 10.1016/j.cllc.2020.10.018. Epub 2020 Nov 2.

  PMID: 33234490 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Carcinoma, Neuroendocrine; Small Cell Lung Carcinoma; Lung Neoplasms; Neuroendocrine Tumors

Interventions

Nivolumab; Temozolomide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; 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; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dwight Owen, MD, MS

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 29, 2018
• First Posted: November 2, 2018
• Study Start: December 31, 2018
• Primary Completion: December 17, 2025
• Study Completion (Estimated): October 31, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)