Sirolimus and Durvalumab for the Treatment of Stage I-IIIA Non-small Cell Lung Cancer

NCT04348292 | Terminated Phase 1 Results DMC FDA Drug

• 5 other identifiers: IRB00116422NCI-2019-07427Winship4867-19P30CA138292P50CA217691
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This trial studies the side effects of sirolimus and durvalumab and to see how well they work in treating patients with stage I-IIIA non-small cell lung cancer. Sirolimus is an oral medication that blocks the mTOR cellular pathway which may help the immune system work better. 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. Giving sirolimus before durvalumab may help the immune system get rid of cancer.

Conditions

Lung Non-Small Cell Carcinoma; Stage I Lung Cancer AJCC v8; Stage IA1 Lung Cancer AJCC v8; Stage IA2 Lung Cancer AJCC v8; Stage IA3 Lung Cancer AJCC v8; Stage IB Lung Cancer AJCC v8; Stage II Lung Cancer AJCC v8; Stage IIA Lung Cancer AJCC v8; Stage IIB Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0

  Other adverse events will be listed and summarized by severity, seriousness, and by system organ class. The number and percentage of subjects who experience AEs will be presented in tabular and/or graphical format and summarized descriptively, where appropriate. The frequency of overall toxicity, categorized by toxicity grades 1 through 5, will be described.

  at time of surgery

• Complete Pathologic Response

  Disappearance of all invasive cancer

  at time of surgery

Other Outcomes (1)

• Number of Participants With Dose Limiting Toxicity (DLT)

  at time of surgery

Study Arms (1)

Treatment (sirolimus, durvalumab)

EXPERIMENTAL

Patients receive sirolimus PO QD on days 1-21 in the absence of disease progression or unacceptable toxicity. Starting on day 22, patients receive durvalumab IV over 1 hour. Treatment with durvalumab repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Within a 2-3 week period after the second dose of durvalumab, but not earlier than two weeks after the administration of durvalumab, patients undergo standard of care surgery.

Drug: Durvalumab; Drug: Sirolimus

Interventions

Durvalumab DRUG

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

Treatment (sirolimus, durvalumab)

Sirolimus DRUG

Given PO

Also known as: AY 22989, RAPA, Rapamune, Rapamycin, SILA 9268A, WY-090217

Treatment (sirolimus, durvalumab)

Eligibility Criteria

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

You may qualify if:

• Patients with pathologically documented NSCLC: Stage I, II, IIIa NSCLC based on 8th edition of American Joint Committee on Cancer (AJCC) Non-small cell Lung Cancer Staging system
• 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. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the United States \[US\]) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \>= 26 weeks
• Body weight \> 30 kg
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 x 10\^9/L (\>= 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)
• 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) 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 for 12 months or more following cessation of all 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)
• 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:

• Patients who have had prior therapy for lung cancer including chemotherapy, hormonal therapy, or radiotherapy
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study
• Prior treatment with anti-PD-1, anti-PDL-1, other PD-1/PDL-1 pathway targeting agents, or mTOR inhibition
• History of allogenic organ transplantation
• 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 \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). 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
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease \>= 5 years before the first dose of investigational product (IP) 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

Sponsors & Collaborators

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

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab; Immunoglobulin G; Disulfides; Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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; Organic Chemicals; Macrolides; Lactones

Limitations and Caveats

This was a low accruing trial which amassed fewer patients than anticipated. Due to stalled enrollment, the study was terminated and did not reach completion.

Results Point of Contact

• Title: Jennifer Carlisle, MD
• Organization: Emory University

jennifer.w.carlisle@emory.edu

404-778-2304

Study Officials

• Jennifer W Carlisle, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 20, 2020
• First Posted: April 16, 2020
• Study Start: January 22, 2021
• Primary Completion: November 4, 2022
• Study Completion: November 4, 2022
• Last Updated: August 22, 2024
• Results First Posted: August 22, 2024

Record last verified: 2024-08

Locations

US (1)