A Phase II Study of Concurrent Chemoradiation Plus Durvalumab (MEDI4736) Followed by Surgery Followed by Adjuvant Durvalumab (MEDI4736) in Medically Operable Patients With Surgically Resectable Stage III (N2) Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Greg Durm, MD
- Enrollment
- 7
- Locations
- 4
- Primary Endpoint
- Pathologic Complete Response Rate
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Greg Durm, MD
Sponsor-Investigator
Hoosier Cancer Research Network
Eligibility Criteria
Inclusion Criteria
- •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)N2M
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Treatment
Neoadjuvant chemotherapy(Durvalumab, Paclitaxel, Carboplatin), radiation and immunotherapy (durvalumab) followed by surgical resection followed by adjuvant immunotherapy (durvalumab)
Intervention: Durvalumab
Treatment
Neoadjuvant chemotherapy(Durvalumab, Paclitaxel, Carboplatin), radiation and immunotherapy (durvalumab) followed by surgical resection followed by adjuvant immunotherapy (durvalumab)
Intervention: Paclitaxel
Treatment
Neoadjuvant chemotherapy(Durvalumab, Paclitaxel, Carboplatin), radiation and immunotherapy (durvalumab) followed by surgical resection followed by adjuvant immunotherapy (durvalumab)
Intervention: Carboplatin
Treatment
Neoadjuvant chemotherapy(Durvalumab, Paclitaxel, Carboplatin), radiation and immunotherapy (durvalumab) followed by surgical resection followed by adjuvant immunotherapy (durvalumab)
Intervention: Radiation
Treatment
Neoadjuvant chemotherapy(Durvalumab, Paclitaxel, Carboplatin), radiation and immunotherapy (durvalumab) followed by surgical resection followed by adjuvant immunotherapy (durvalumab)
Intervention: Surgical Resection
Outcomes
Primary Outcomes
Pathologic Complete Response Rate
Time Frame: 3 months
Pathologic Complete Response Rate is defined as lack of evidence of viable cancer in the surgical specimen at the time of surgery.
Secondary Outcomes
- Disease Free Survival (DFS)(Time from surgical resection until disease recurrence or death, up to a maximum of 8 months)
- 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.)