Durvalumab (MEDI4736) With or Without SBRT in Clinical Stage I, II and IIIA Non-small Cell Lung Cancer

NCT02904954 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1501015795
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out the effectiveness of the drug durvalumab (MEDI4736) with or without stereotactic body radiation therapy (SBRT) as treatment for stage I (tumors \> 2cm), II, and IIIA non-small cell lung cancer (NSCLC) prior to surgery and one year following surgery.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Lung neoplasms; Bronchial Neoplasms; Carcinoma, bronchogenic; Neoplasms; Neoplasms by site; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Major Pathological Response (MPR)

  MPR is defined as ≤10% residual viable tumor in the resected specimen.

  Durvalumab start date to surgical resection, up to 10 weeks

Secondary Outcomes (2)

• Kaplan-Meier Disease-Free Survival Proportion at 2 Years

  From date of Durvalumab start date until the date of first documented progression or date of death from any cause, whichever came first, assessed every 6 months for 2 years.

• Objective Clinical Response Rate

  Treatment day 1 up to weeks 6-7

Other Outcomes (1)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v. 4.0

  Up to 72 weeks

Study Arms (2)

Arm 1 (Durvalumab monotherapy)

EXPERIMENTAL

Durvalumab (MEDI4736) 1.12 g administered pre-operatively every 3 weeks for 2 cycles followed by surgical resection. Durvalumab monotherapy 1.5 g will be given for 12 months post-operatively.

Drug: Durvalumab

Arm 2 (Durvalumab plus SBRT)

EXPERIMENTAL

Durvalumab (MEDI4736) 1.12 g administered pre-operatively every 3 weeks for 2 cycles plus radiotherapy delivered in 3 daily fractions starting concurrently with the first cycle of durvalumab (MEDI4736) followed by surgical resection. Durvalumab monotherapy 1.5 g will be given for 12 months post-operatively.

Drug: Durvalumab; Other: Durvalumab plus SBRT

Interventions

Durvalumab DRUG

Intravenously

Also known as: MEDI4736

Arm 1 (Durvalumab monotherapy); Arm 2 (Durvalumab plus SBRT)

Durvalumab plus SBRT OTHER

Intravenously plus radiotherapy

Also known as: MEDI4736

Arm 2 (Durvalumab plus SBRT)

Eligibility Criteria

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

You may qualify if:

• Patient has histologically or cytologically proven clinical stages I (tumors \> 2 cm), II, and IIIA NSCLC and is considered eligible for surgical resection with curative intent. Patients with 2 primary non-small cell lung cancers are allowed.
• Measureable disease, as defined by RECIST v1.1.
• Written informed consent and HIPAA obtained from the subject prior to performing any protocol-related procedures.
• Age \> 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects 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.
• AST (SGOT)/ALT (SGPT), and alkaline phosphatase ≤ 2.5 x institutional upper limit of normal (ULN).
• Serum creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 3 weeks.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ, in-situ urinary bladder cancer , treated localized prostate cancer and ductal carcinoma-in situ.
• Indolent hematological malignancies
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal,inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). No active diverticulitis within the previous 3 months. 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

• Weill Medical College of Cornell University: lead
• AstraZeneca: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Related Publications (3)

• Altorki NK, Walsh ZH, Melms JC, Port JL, Lee BE, Nasar A, Spinelli C, Caprio L, Rogava M, Ho P, Christos PJ, Saxena A, Elemento O, Bhinder B, Ager C, Amin AD, Sanfilippo NJ, Mittal V, Borczuk AC, Formenti SC, Izar B, McGraw TE. Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I-III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial. Nat Commun. 2023 Dec 19;14(1):8435. doi: 10.1038/s41467-023-44195-x.

  PMID: 38114518 DERIVED

• Lee B, Mynard N, Nasar A, Villena-Vargas J, Chow O, Harrison S, Stiles B, Port J, Altorki N. Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non-small cell lung cancer: Results from a randomized trial. J Thorac Cardiovasc Surg. 2023 Jan;165(1):327-334.e2. doi: 10.1016/j.jtcvs.2022.07.017. Epub 2022 Aug 6.

  PMID: 36028357 DERIVED

• Altorki NK, McGraw TE, Borczuk AC, Saxena A, Port JL, Stiles BM, Lee BE, Sanfilippo NJ, Scheff RJ, Pua BB, Gruden JF, Christos PJ, Spinelli C, Gakuria J, Uppal M, Binder B, Elemento O, Ballman KV, Formenti SC. Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial. Lancet Oncol. 2021 Jun;22(6):824-835. doi: 10.1016/S1470-2045(21)00149-2. Epub 2021 May 18.

  PMID: 34015311 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Bronchial Neoplasms; Carcinoma, Bronchogenic; Neoplasms; Neoplasms by Site; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms

Interventions

durvalumab; Radiosurgery

Condition Hierarchy (Ancestors)

Lung Diseases; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Cathy Spinelli, RN BSN
• Organization: Weill Cornell Medicine

caf2007@med.cornell.edu

212-746-3328

Study Officials

• Nasser K Altorki, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 18, 2016
• First Posted: September 19, 2016
• Study Start: December 2, 2016
• Primary Completion: September 16, 2020
• Study Completion: October 4, 2022
• Last Updated: October 11, 2023
• Results First Posted: August 3, 2021

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)