Nivolumab After Cyclophosphamide and Doxorubicin Induction Therapy in NSCLC With PD-L1<10%

NCT03808480 | Unknown Phase 2 FDA Drug

• 1 other identifier: NCC2018-0267
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Nivolumab is now the standard of care for second-line treatment of advanced squamous or nonsquamous NSCLC regardless of the tumor's expression of PD-1L. CheckMate057 trial results showed that in unselected patients with advanced or recurrent nonsquamous NSCLC who had stopped responding to a platinum-based chemotherapy regimen, treatment with nivolumab produced significantly better overall survival during follow-up as long as 18 months, compared with a docetaxel-based regimen. But during the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab. A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1. In addition, only a subgroup of patients benefits from nivolumab with response rates of 20% in unselected cohorts and 10% in low PD-L1 expression cohort. Strategies to render the tumor micro-environment (TME) more susceptible to anti-PD1 might include stimulation of anti-cancer immune responses by induction treatment with low dose chemotherapy. Given the potent immune-modulating effects and anti-tumor activity of cyclophosphamide and doxorubicin, Investigator propose a study of combining nivolumab with induction therapy with cyclophosphamide and doxorubicin for nonsquamous NSCLC with PD-L1 expression less than 10%.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• objective response

  objective response rate using RECIST v1.1

  From date of first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48months

Study Arms (1)

CA and Nivolumab

EXPERIMENTAL

After 1 cycle of cyclophosphamide and doxorubicin (CA) induction therapy, Nivolumab 360mg flat dose will be given on day 1 with CA chemotherapy in a 21-day cycle. After the completion of 4 cycles of CA chemotherapy, Nivolumab will be continued as a single agent at a dose of 480mg flat dose every 4 weeks until loss of clinical benefit

Drug: CA and Nivolumab

Interventions

CA and Nivolumab DRUG

Cyclophosphamide 500mg/m2 IV on D1 (C1-4), 1cycle=21days) Doxorubicin 50mg/m2 IV on D1 (C1\~4, 1cycle=21days) Nivolumab 360 mg/IV C2\~4 D1 (1cycle=21days) Nivolumab 400mg/IV on D1 from Cycle 5 every 4 weeks.

Also known as: Opdivo

CA and Nivolumab

Eligibility Criteria

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

You may qualify if:

• Histologic or cytologic diagnosis of nonsquamous NSCLC with SP263 PD-L1 expression \<10%
• Patients whose tumor is not known to have anaplastic lymphoma kinase(ALK) or epidermal growth factor receptor(EGFR) mutation and Previously treated with at least one platinum-based chemotherapy but less than 3 prior chemotherapy
• Before study entry, a minimum of 21 days must have elapsed since any prior chemotherapy.
• Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease.
• No other forms of cancer therapy, such as immunotherapy for at least 2 weeks before the enrollment in study.
• Performance status of 0-1 on the ECOG criteria.
• At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (Revised RECIST guideline version 1.1)
• Estimated life expectancy of at least 8 weeks.
• Patient compliance that allow adequate follow-up. Adequate hematologic (WBC ≥4,000/mm3 또는 4.0 x 103/㎕ Platelet count ≥130,000mm3 또는 130 x 103/㎕ Bilirubin total ≤1.0 mg/dL AST/ALT≤ 80 IU/L creatinine concentration 1XULN or creatinine clearance (CrCl) \> 50 mL/min (measured using the Cockcroft-Gault formula)
• Informed consent from patient or patient's relative.
• Males or females at least 18 years of age.

You may not qualify if:

• Previous therapy with anti-PD-1 or -PD-L1 inhibitors
• Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy
• Has received prior chemotherapy or tyrosine kinase inhibitor therapy within 3 weeks of the first dose of trial treatment ; completed palliative radiotherapy(except for brain and extremities) within 2weeks of the first dose of trial treatment. Prior curative thoracic radiation therapy(\>=60Gy) is permitted if disease progression occured \>4weeks after the completion of therapy.
• Treatment with other investigational drugs or treatment in another clinical trial within the past three weeks before start of therapy or concomitantly with this trial
• Has received a live vaccine(Concomitant yellow fever vaccin) within 4 weeks prior to the first administration of study medication. Concomitant yellow fever vaccination
• Active CNS metastases
• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for 2 weeks prior to randomization
• Leptomeningeal disease
• Significant cardiovascular diseases (i.e., hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 12 months, congestive heart failure \> NYHA II, serious cardiac arrhythmia, pericardial effusion)
• Proteinuria CTCAE grade 2 or greater
• Significant weight loss (\> 10 %) within the past 6 weeks prior to treatment in the present trial
• Current peripheral neuropathy ≥ CTCAE(version4.0) Grade 2 except due to trauma
• Major injuries and/or surgery with incomplete wound healing within the past ten days prior to enrollment
• Serious infections requiring systemic antibiotic (e.g. antiviral, antimicrobial, antifungal) therapy
• Active hepatitis C and/or B infection

Sponsors & Collaborators

• National Cancer Center, Korea: lead

Study Sites (1)

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab

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

Study Officials

• Ji-youn han, Ph.D

  National Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ji-youn Han, Ph.D

CONTACT

82-31-920-1210; jymama@ncc.re.kr

Sehee Oh

CONTACT

82-31-920-0398; oshee97@ncc.re.kr

Study Design

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

Study Record Dates

• First Submitted: December 26, 2018
• First Posted: January 17, 2019
• Study Start: January 23, 2019
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: April 6, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)