Platinum-Based Chemotherapy and Durvalumab for the Treatment of Stage IIIB or IV Non-small Cell Lung Cancer

NCT04262869 | Withdrawn Phase 2 DMC FDA Drug

• 4 other identifiers: IRB00114607NCI-2019-06508Winship4802-19P30CA138292
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies how well platinum-based chemotherapy works when given together with durvalumab in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, 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. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to find out if the combination of chemotherapy in combination with the immune therapy drug durvalumab would be efficacious and have an acceptable toxicity profile in patients with advanced non-small cell lung cancer.

Conditions

Lung Non-Small Cell Carcinoma; Stage IIIB Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• 6-months progression-free survival (PFS) rate

  Will be calculated as proportion along with 95% confidence intervals (CI) using the Clopper-Pearson method. Chi-square test or Fisher's exact test will be used to compare the 6-months PFS rate between the different groups stratified by different factors, respectively. Logistics regression model will be further employed to test the adjusted effect of each factor on 6-month PFS rate after adjusting for other clinical factors and demographic factors.

  6 months

Secondary Outcomes (3)

• Overall survival (OS)

  Up to 5 years

• PFS

  Up to 5 years

• Incidence of adverse events (AEs)

  Up to 90 days post treatment

Study Arms (2)

Arm I (squamous NSCLC)

EXPERIMENTAL

Patients receive carboplatin IV over 15-60 minutes, paclitaxel IV over 3 hours and durvalumab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who do not progress receive durvalumab IV every 4 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Biological: Durvalumab; Drug: Paclitaxel

Arm II (non-squamous NSCLC)

EXPERIMENTAL

Patients receive carboplatin IV over 15-60 minutes, pemetrexed IV over 10 minutes and durvalumab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who do not progress receive durvalumab IV and pemetrexed IV every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Biological: Durvalumab; Drug: Pemetrexed

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (squamous NSCLC); Arm II (non-squamous NSCLC)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Arm I (squamous NSCLC); Arm II (non-squamous NSCLC)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (squamous NSCLC)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate

Arm II (non-squamous NSCLC)

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Have a histologically confirmed or cytologically confirmed diagnosis of stage IIIB or stage IV NSCLC
• Have a performance status of 2 on the Eastern Cooperative Oncology Group (ECOG) performance status with any age, or age \>= 70 with ECOG PS of 0, 1, or 2, on the day of signing informed consent
• Patients must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by local site investigator/radiology assessment. Target lesions situated in previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• Have not received prior systemic treatment for their advanced/metastatic NSCLC. Subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease
• Body weight \> 30 kg
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) \>= 1.5 (\>= 1500 per mm\^3)
• Platelet count \>= 100) x 10\^9/L (\>= 100,000 per mm\^3)
• Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed if =\< 3.0 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =\< 5 x ULN
• Measured creatinine clearance (CL) \> 40 mL/min or calculated creatinine CL \> 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
• The effects of the study drug on the developing human fetus are unknown. For this reason female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
• FCBP and men must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study participation and for at least 4 months following study drug discontinuation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (if age \> 55 years); if the female subject is \< 55 years and she has been naturally postmenopausal for \> 1 year her reproductive status has to be verified by additional lab tests (\< 20 estradiol OR estradiol \< 40 with follicle stimulating hormone \[FSH\] \> 40 in women not on estrogen replacement therapy)
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 4 weeks
• ECOG PS 3 or higher
• Prior systemic therapy for the treatment of advanced or metastatic NSCLC
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Completed palliative radiotherapy within 7 days of the first dose of trial treatment
• Has a known sensitivity to any component of carboplatin, pemetrexed, paclitaxel, or durvalumab
• Is unable to unwilling to take folic acid of vitamin b12 supplementation (if non-squamous histology)
• Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician
• Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
• History of allogenic organ transplantation
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Carboplatin; durvalumab; Immunoglobulin G; Disulfides; Paclitaxel; Taxes; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Conor E Steuer

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 10, 2020
• Study Start: March 27, 2020
• Primary Completion: October 18, 2021
• Study Completion: October 18, 2021
• Last Updated: October 27, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share