Chemoradiation Plus Durvalumab Followed by Surgery Followed by Adjuvant Durvalumab in Patients With Surgically Resectable Stage III (N2) Non-Small Cell Lung Cancer

NCT03871153 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN LUN17-321
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open label, multi-institutional, single arm Phase II trial. All patients will be treated with Carboplatin, Paclitaxel, Durvalumab and Radiation. All patients with non-PD after induction therapy who remain surgical candidates will undergo surgical resection 4-12 weeks following induction therapy. After surgical resection, all patients who remain eligible will be treated with adjuvant Durvalumab every 4 weeks for 6 cycles beginning 4-12 weeks after surgical resection.

Conditions

Non Small Cell Lung Cancer; Stage III Non-small-cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response Rate

  Pathologic Complete Response Rate is defined as lack of evidence of viable cancer in the surgical specimen at the time of surgery.

  3 months

Secondary Outcomes (3)

• Pathologic N0 Rate

  3 months

• Assess Adverse Events (AE)

  AEs had been recorded from time of signed informed consent until 90 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 13 months.

• Disease Free Survival (DFS)

  Time from surgical resection until disease recurrence or death, up to a maximum of 8 months

Study Arms (1)

Treatment

OTHER

Neoadjuvant chemotherapy(Durvalumab, Paclitaxel, Carboplatin), radiation and immunotherapy (durvalumab) followed by surgical resection followed by adjuvant immunotherapy (durvalumab)

Device: Durvalumab; Drug: Paclitaxel; Drug: Carboplatin; Radiation: Radiation; Procedure: Surgical Resection

Interventions

Durvalumab DEVICE

Neoadjuvant Durvalumab 750 mg IV on Days 1, 15 and 29 Adjuvant Durvalumab 12 weeks after undergoing surgical resection 1,500 mg IV on Day 1

Also known as: Imfinzi

Treatment

Paclitaxel DRUG

Paclitaxel 45 mg/m2 IV Days 1, 8, 15, 22, 29 and +/- 36

Also known as: Taxol

Treatment

Carboplatin DRUG

Carboplatin AUC of 2 IV Days 1, 8, 15, 22, 29 +/- 36

Also known as: Platinol

Treatment

Radiation RADIATION

1.8-2.0 Gy per day (5 days/week) for a total of 45-61.2 Gy over 5-6 weeks. Treatment will be delivered using IMRT or 3DCRT using typically 6-10MV photons. Proton therapy is also allowed. 4D simulation and appropriate IGRT are encouraged. Radiation therapy must begin within one week of the first day of chemotherapy (or vice versa).

Treatment

Surgical Resection PROCEDURE

Patients will undergo repeat imaging between 4 and 12 weeks after completing neoadjuvant therapy. Those without evidence of progressive disease and found to be a surgical candidate by a thoracic surgeon will undergo surgical resection between 4 and 12 weeks after neoadjuvant therapy.

Treatment

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0 or 1 within 28 days prior to registration.
• Histological or cytological confirmation of NSCLC (Adenocarcinoma, Squamous Cell Carcinoma, Large Cell Carcinoma). A pathology report (from the last 6 months) confirming the diagnosis of NSCLC must be obtained and reviewed by the treating physician prior to registration to study.
• Must have resectable and medically operable stage III (N2) NSCLC with clinical or biopsy-proven N2 disease. If patients have clinical N2 disease they need to be biopsy-proven (with EBUS or mediastinoscopy) during screening and have confirmed prior to study enrollment). Subjects must be considered resectable and medically operable based on the judgment of the treating physician. Stage III (N2) defined as per the 7th edition of the TNM staging system (T1a, T1b, T1c, T2a, T2b, T3, or T4)N2M0.
• Individuals cannot have contralateral neck or contralateral mediastinum nodal involvement.
• Subjects must have a life expectancy of at least 12 weeks to qualify.
• Individuals must not have distant metastasis, defined as M0 in the TMN staging system.
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration.
• Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
• Hemoglobin (Hgb) ≥ 9 g/dL (may be transfused)
• Platelets ≥100,000/mcl
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 x upper limit of normal (ULN) OR ≥ 40 mL/min for subjects with creatinine levels \>1.5 x institutional ULN
• Bilirubin ≤ 1.5 × ULN OR Direct bilirubin of ≤ ULN for subjects with total bilirubin levels of \>1.5x ULN
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN if no liver metastases

You may not qualify if:

• History of a major surgical procedure (as defined by investigator) within 28 days prior to the first dose of study drug. NOTE: Local surgery for isolated lesions for palliative intent is acceptable.
• History of another primary malignancy except for a) malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study drug, b) adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, c) adequately treated carcinoma in situ without evidence of disease.
• History of leptomeningeal disease.
• Persons who have small cell carcinoma.
• Persons who do not meet the Stage IIIA NSCLC classification criteria outlined above.
• Presence of superior vena cava syndrome.
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment.
• Active central nervous system (CNS) metastases. Subjects must undergo a head computed tomography (CT) scan or brain MRI within 42 days prior to registration for protocol therapy to exclude brain metastases if symptomatic or without prior brain imaging.
• Treatment with any investigational agent within 28 days prior to registration for protocol therapy.
• Patients should not have received any prior therapy for the current diagnosis of NSCLC. Treatments done for previously diagnosed malignancies are permitted. Prior therapy with a PD-1, PD-L1 (including Durvalumab), PD-L2 or CTLA-4 inhibitor or a lung cancer-specific vaccine therapy are not permitted.
• Presence of metastatic disease (stage IV NSCLC) is not allowed. Subjects must be evaluated with a CT or PET scan prior to registration for protocol therapy to exclude metastatic disease.
• 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

Sponsors & Collaborators

• Greg Durm, MD: lead
• AstraZeneca: collaborator
• Indiana University School of Medicine: collaborator

Study Sites (4)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University Melvin and Bren Simon

Indianapolis, Indiana, 46202, United States

Location

New York University Clinical Cancer Center

New York, New York, 10016, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Paclitaxel; Carboplatin; Cisplatin; Radiation

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Physical Phenomena

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Greg A Durm, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 5, 2019
• First Posted: March 12, 2019
• Study Start: August 2, 2019
• Primary Completion: October 30, 2021
• Study Completion: March 9, 2022
• Last Updated: November 1, 2023
• Results First Posted: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)