RECRUITING

Durvalumab and Tremelimumab in Combination With Chemotherapy in HIV-infected Patients With Non-small Cell Lung Cancer

Conditions

Carcinoma, Non-Small Cell Lung Lung Cancer Non-Small Cell Lung Cancer Durvalumab Tremelimumab

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase II trial of durvalumab and tremelimumab in combination of platinum-based chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human immunodeficiency virus (HIV) infection will be eligible. Patients will receive standard platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. It is hypothesized that Durvalumab and tremelimumab in combination with standard chemotherapy is safe and effective for the treatment of stage IV NSCLC in patients with HIV infection.

Official Title

A Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab in Combination With Chemotherapy in HIV-infected Patients With Non-small Cell Lung Cancer

Quick Facts

Study Start:2020-12-09

Study Completion:2024-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04499053

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patients with stage IV NSCLC who had undergone no previous systemic therapy for stage IV disease. 2. Patients with HIV must be on an effective combination anti-retroviral therapy (cART) regimen for ≥ 4 weeks. Also, patients need to meet the following criteria. * Documented HIV viral load \< 400 copies/mL * No AIDS-defining opportunistic infections within the last 12 months * No concurrent incurable AIDS-defining malignancy 3. Age \> 18 years at time of study entry. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 5. Body weight \>30kg 6. Adequate normal organ and marrow function as defined below: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥ 1,000 per mm3 * Platelet count ≥ 100,000 per mm3 * CD4 T-cell count ≥ 100 per mm3 for HIV-infected patients * 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. * AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x 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: 7. 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). 8. 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. 9. Must have a life expectancy of at least 12 weeks.	1. Sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q) and/or ALK translocations by locally approved laboratory testing including blood-based liquid biopsy. 2. 2. Coinfection of HIV + HBV (coinfection of HIV and HBV allowed if the patient is on appropriate anti-viral therapy for HBV) or HIV + HCV (coinfection of HIV and HCV allowed if HCV is cured or patient is on appropriate anti-viral therapy for hepatitis C). Coinfection of HBV and HCV is allowed if otherwise eligible. 3. No measurable disease. 4. Receipt of the last dose of anticancer therapy (chemotherapy, targeted therapy) ≤ 21 days prior to the first dose of study treatment. 5. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy (chemotherapy, targeted therapy, radiation therapy) with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. 6. Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks before treatment (no washout period is required for patients who have received stereotactic body radiation therapy). 7. Subject has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study drug or has not recovered from side effects of such procedure (≥ grade 2 AE related to such procedure). Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and subject can be enrolled in the study ≥ 1 week after the procedure. 8. History of allogenic organ transplantation. 9. 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: 10. 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, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. 11. Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. 12. Previously untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks before treatment (no washout period is required for patients who have received stereotactic body radiation therapy). 13. Active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice). 14. Current or prior use of immunosuppressive medication within 7 days before the first dose of durvalumab. The following are exceptions to this criterion: 15. Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product (IP). Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of IP. 16. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control. 17. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 18. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 within 12 months of the first dose of durvalumab. 19. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.

Inclusion Criteria

Exclusion Criteria

1. Patients with stage IV NSCLC who had undergone no previous systemic therapy for stage IV disease.
2. Patients with HIV must be on an effective combination anti-retroviral therapy (cART) regimen for ≥ 4 weeks. Also, patients need to meet the following criteria.
* Documented HIV viral load \< 400 copies/mL
* No AIDS-defining opportunistic infections within the last 12 months
* No concurrent incurable AIDS-defining malignancy
3. Age \> 18 years at time of study entry.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
5. Body weight \>30kg
6. Adequate normal organ and marrow function as defined below:
* Hemoglobin ≥ 9.0 g/dL
* Absolute neutrophil count (ANC) ≥ 1,000 per mm3
* Platelet count ≥ 100,000 per mm3
* CD4 T-cell count ≥ 100 per mm3 for HIV-infected patients
* 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.
* AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x 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:
7. 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).
8. 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.
9. Must have a life expectancy of at least 12 weeks.

1. Sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q) and/or ALK translocations by locally approved laboratory testing including blood-based liquid biopsy.
2. 2. Coinfection of HIV + HBV (coinfection of HIV and HBV allowed if the patient is on appropriate anti-viral therapy for HBV) or HIV + HCV (coinfection of HIV and HCV allowed if HCV is cured or patient is on appropriate anti-viral therapy for hepatitis C). Coinfection of HBV and HCV is allowed if otherwise eligible.
3. No measurable disease.
4. Receipt of the last dose of anticancer therapy (chemotherapy, targeted therapy) ≤ 21 days prior to the first dose of study treatment.
5. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy (chemotherapy, targeted therapy, radiation therapy) with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
6. Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks before treatment (no washout period is required for patients who have received stereotactic body radiation therapy).
7. Subject has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study drug or has not recovered from side effects of such procedure (≥ grade 2 AE related to such procedure). Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and subject can be enrolled in the study ≥ 1 week after the procedure.
8. History of allogenic organ transplantation.
9. 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:
10. 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, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
11. Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
12. Previously untreated central nervous system (CNS) metastases or leptomeningeal disease. Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks before treatment (no washout period is required for patients who have received stereotactic body radiation therapy).
13. Active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice).
14. Current or prior use of immunosuppressive medication within 7 days before the first dose of durvalumab. The following are exceptions to this criterion:
15. Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product (IP). Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of IP.
16. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control.
17. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
18. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4 within 12 months of the first dose of durvalumab.
19. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.

Contacts and Locations

Principal Investigator

Chul Kim, MD

STUDY_CHAIR

Georgetown University

Study Locations (Sites)

Georgetown Lombardi Comprehensive Cancer Center

Washington, District of Columbia, 20007

United States

Medstar Washington Hospital Center

Washington, District of Columbia, 20010

United States

Harry and Jeannette Weinberg Cancer Institute at Franklin Square

Baltimore, Maryland, 21237

United States

Collaborators and Investigators

Sponsor: Georgetown University

Chul Kim, MD, STUDY_CHAIR, Georgetown University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-09

Study Completion Date2024-12

Study Record Updates

Study Start Date2020-12-09

Study Completion Date2024-12

Terms related to this study

Keywords Provided by Researchers

Lung Cancer
Non-Small Cell Lung Cancer
Durvalumab
Tremelimumab

Additional Relevant MeSH Terms

Carcinoma, Non-Small Cell Lung