Local Consolidative Therapy and Durvalumab for Oligoprogressive and Polyprogressive Stage III NSCLC After Chemoradiation and Anti-PD-L1 Therapy

NCT04892953 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2020-1031NCI-2021-03777
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial finds out the effect of local consolidative therapy and durvalumab in treating patients with stage III non-small cell lung cancer that has 3 or fewer lesions of progression (oligoprogressive) and greater than 3 lesions of progression (polyprogressive) after chemoradiation and anti-PD-l1 therapy. Local consolidative therapy, such as surgery and/or radiation, after initial treatment may kill any remaining tumor cells. Immunotherapy with durvalumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving local consolidative therapy and durvalumab may help to control the disease.

Conditions

Stage III Lung Cancer AJCC v8; Stage III Lung Non-Small Cell Cancer AJCC v7; Stage IIIA Lung Cancer AJCC v8; Stage IIIA Lung Non-Small Cell Cancer AJCC v7; Stage IIIB Lung Cancer AJCC v8; Stage IIIB Lung Non-Small Cell Cancer AJCC v7; Stage IIIC Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  The Kaplan-Meier product-limit estimate of the PFS function will be estimated and displayed for each treatment group. The median PFS time will be given with 95% confidence interval. Summaries of the number and percentage of patients experiencing a PFS event, and the type of event (Response Evaluation Criteria in Solid Tumors version 1.1 or death) will be provided. As comparative analysis, the one-sample log-rank test will be used to test difference in PFS between treatment and the historical control.

  From local consolidative therapy (LCT) initiation until progression or death, assessed up to 2 years

Secondary Outcomes (6)

• Overall survival (OS)1

  From diagnosis to death, assessed up to 2 years

• OS2

  From LCT initiation until death, assessed up to 2 years

• Rate of intralobar progression

  Up to 2 years

• Rate of mediastinal progression

  Up to 2 years

• Rate of distant progression

  Up to 2 years

Study Arms (2)

Cohort A (oligoprogressive)

EXPERIMENTAL

Patients undergo LCT consisting of radiation therapy and/or surgery, then receive durvalumab IV over 1 hour on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Durvalumab; Procedure: Local Consolidation Therapy; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Cohort B (polyprogressive)

EXPERIMENTAL

Patients undergo LCT consisting of radiation therapy and/or surgery, then receive durvalumab IV over 1 hour on day 1. Patients also receive one of the following chemotherapy options: carboplatin and paclitaxel on day 1, carboplatin on day 1 and nab-paclitaxel on days 1, 8, 15, or carboplatin on day 1 and gemcitabine on days 1 and 8. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with non-squamous histology receive pemetrexed on day 1 every 21 days for cycles 1-4, pemetrexed and durvalumab IV on day 1 every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Biological: Durvalumab; Drug: Gemcitabine; Procedure: Local Consolidation Therapy; Drug: Nab-paclitaxel; Drug: Paclitaxel; Drug: Pemetrexed; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

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

Cohort B (polyprogressive)

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

Cohort A (oligoprogressive); Cohort B (polyprogressive)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Cohort B (polyprogressive)

Local Consolidation Therapy PROCEDURE

Undergo LCT

Also known as: LCT, Local Consolidative Therapy

Cohort A (oligoprogressive); Cohort B (polyprogressive)

Nab-paclitaxel DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Protein-bound Paclitaxel

Cohort B (polyprogressive)

Paclitaxel DRUG

Given IV

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

Cohort B (polyprogressive)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate, Pemfexy

Cohort B (polyprogressive)

Quality-of-Life Assessment OTHER

Complete questionnaire

Also known as: Quality of Life Assessment

Cohort A (oligoprogressive); Cohort B (polyprogressive)

Questionnaire Administration OTHER

Complete questionnaire

Cohort A (oligoprogressive); Cohort B (polyprogressive)

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
• Stage III NSCLC (AJCC 7th and 8th edition) patients who received standard chemoradiation followed by durvalumab therapy with either progressive disease or persistent disease. Persistent disease defined as residual positron emission tomography (PET) avidity 6 months after completion of initial definitive therapy and confirmed with biopsy
• For lung adenocarcinoma patients, patients must not harbor any EGFR sensitizing mutations, ALK fusion, ROS1 rearrangements, RET fusions, or MET exon 14 skipping mutations where there are standard of care therapy options available. For patients with histologies other than adenocarcinoma, EGFR and ALK status is not required. Adenocarcinoma patients may be consented prior to the EGFR, ALK, and ROS1 status being known, but EGFR, ALK, and ROS1 status must be determined prior to initiating therapy. EGFR, ALK, and ROS ALK status may be determined using either tumor- or plasma-based, Clinical Laboratory Improvement Act (CLIA)-certified assays. For patients with NSCLC, not otherwise specified (NOS), EGFR testing is not required, as the frequency of alterations is exceedingly rare in this histology
• Cohort A: Oligoprogressive disease is defined as having 3 or fewer lesions of progression (sites can be local, distant, or both). Multiple mediastinal lesions will be counted as 1 lesion
• Cohort B: Polyprogressive disease defined as having greater than 3 lesions of progression (sites can be local, distant, or both). Multiple mediastinal lesions will be counted as 1 lesion
• Candidate for radiation therapy to at least one lesion
• Tumor assessment by computed tomography (CT) scan with contrast chest/abdomen/pelvis or PET-CT, and magnetic resonance imaging (MRI) brain must be performed within 28 days prior to study entry
• Age \>= 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Body weight \> 30 kg
• Hemoglobin \>= 9.0 g/dL
• Platelet count \>= 75 × 10\^9/L
• 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 only in consultation with their physician
• 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) \> 15 mL/min or calculated creatinine CL \> 15 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance

You may not qualify if:

• Patients who rapidly progressed on the PACIFIC regimen (chemoradiotherapy \[CRT\] + durvalumab). This is defined as any progression on the first 3-month imaging scan after starting durvalumab post-CRT
• Patients who were treated with anti-PD-(L)1 therapy other than durvalumab
• Participation in another clinical study with an investigational product during the last 4 weeks
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study. No other investigational therapy is permitted after durvalumab and start of this protocol
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) =\< 28 days prior to the first dose of study drug. This 28 day washout period is not required for durvalumab. If sufficient wash-out time has not occurred due to the schedule or pharmacokinetic (PK) properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca and the investigator
• 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 (with the exception of protocol directed chemotherapy in the polyprogression cohort), 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 or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Carboplatin; durvalumab; Immunoglobulin G; Disulfides; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes; Paclitaxel; Pemetrexed

Condition Hierarchy (Ancestors)

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; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Economics; Health Care Economics and Organizations; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Joe Y Chang, MD,MS,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 19, 2021
• Study Start: July 7, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (1)