Clinical Trials /

Radiotherapy and Durvalumab/Durvalumab Combo (Tremelimumab/Olaparid) for Small Cell Lung Cancer

NCT03923270

Description:

This is a randomized multi-arm trial evaluating the safety and efficacy of thoracic radiation therapy followed by either durvalumab as monotherapy or in combination with tremelimumab or olaparib in participants with Extensive-Stage Disease Small Cell Lung Cancer (ES-SCLC) who have completed a first-line platinum-based chemotherapy regimen and achieved ongoing complete response (CR), partial response (PR) or stable disease (SD).

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Radiotherapy and Durvalumab/Durvalumab Combo (Tremelimumab/Olaparid) for Small Cell Lung Cancer
  • Official Title: Sequential Maintenance With Thoracic Radiotherapy and Durvalumab (MEDI4736) Monotherapy or Durvalumab (MEDI 4736) Combinations (Tremelimumab or Olaparib) in Patients With Extensive Stage-Small Cell Lung Cancer After First Line Platinum Based Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: MCC-19942
  • NCT ID: NCT03923270

Conditions

  • Small Cell Lung Cancer Extensive Stage
  • Small-cell Lung Cancer

Interventions

DrugSynonymsArms
DurvalumabImfinzi, MEDI4736Thoracic Radiotherapy plus Durvalumab
TremelimumabThoracic Radiotherapy plus Durvalumab and Tremelimumab
Olaparib PillLynparza, MK-7339Thoracic Radiotherapy plus Durvalumab and Olaparib

Purpose

This is a randomized multi-arm trial evaluating the safety and efficacy of thoracic radiation therapy followed by either durvalumab as monotherapy or in combination with tremelimumab or olaparib in participants with Extensive-Stage Disease Small Cell Lung Cancer (ES-SCLC) who have completed a first-line platinum-based chemotherapy regimen and achieved ongoing complete response (CR), partial response (PR) or stable disease (SD).

Trial Arms

NameTypeDescriptionInterventions
Thoracic Radiotherapy plus DurvalumabExperimentalPatients will receive thoracic radiotherapy (30 Gray units total, 3 Gray units X 10 fractions), then in 2-3 weeks begin 1500 mg intravenously of Durvalumab every 4 weeks for up to 13 doses
  • Durvalumab
Thoracic Radiotherapy plus Durvalumab and TremelimumabExperimentalPatients will receive thoracic radiotherapy (30 Gray units total, 3 Gray units X 10 fractions), then in 2-3 weeks begin 1500 mg intravenously of Durvalumab every 4 weeks for up to 4 doses and 75mg intravenously of Tremelimumab every 4 weeks for up to 4 doses
  • Durvalumab
  • Tremelimumab
Thoracic Radiotherapy plus Durvalumab and OlaparibExperimentalPatients will receive thoracic radiotherapy (30 Gray units total, 3 Gray units X 10 fractions), then in 2-3 weeks begin 1500 mg intravenously of Durvalumab every 4 weeks and 300 mg orally of Olaparib twice a day
  • Durvalumab
  • Olaparib Pill

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent

          -  Body weight greater than 30 kg

          -  Participants must be willing and able to comply with scheduled visits, treatment
             schedule, laboratory tests and other requirements of the study.

          -  Participants must have small cell lung cancer, documented by histology or cytology
             from brushing, washing, fine needle aspiration or core biopsy from a defined lesion,
             but not from sputum cytology alone. No mixed histologies allowed.

          -  Participants must be presented at initial diagnosis with extensive-stage disease
             (ES-SCLC).

          -  Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.

          -  Participants must have received 4-6 cycles of platinum-based first-line chemotherapy
             and must have an ongoing complete response (CR), partial response (PR), or stable
             disease (SD) after completion. Acceptable combinations (NCCN guidelines), include
             cisplatin or carboplatin with etoposide or irinotecan. As an exception to the above
             criterion, participants receiving only 3 cycles of chemotherapy due to toxicity are
             eligible, if they have an ongoing PR or CR after the 3rd cycle. Participants who have
             received > 6 cycles of platinum-based first-line chemotherapy are not eligible.
             Participants receiving checkpoint inhibitor (CPI) monotherapy (anti-PD-1, anti-PD-L1,
             others) as part of their first line chemotherapy treatment will be eligible as long as
             they discontinue the CPI prior to the start of thoracic radiotherapy.

          -  Participants must initiate study treatment with thoracic XRT ≤ 60 days from the last
             dose of platinum- based first line chemotherapy;

          -  Whenever possible, a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or
             5-10 unstained slides of tumor sample (archival) should be made available (less
             material is acceptable);

          -  Participants must have a life expectancy of 16 weeks or more.

          -  Active infection including: tuberculosis, hepatitis B (known positive hepatitis B
             surface antigen (HBsAg) result) and/or, hepatitis C. Patients with a past or resolved
             hepatitis B infection (defined as the presence of hepatitis B core antibody [anti-HBc]
             and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody
             are eligible only if polymerase chain reaction is negative for HCV RNA (indicating no
             current infection).

          -  Known positive test for human immunodeficiency virus (positive HIV 1/2 antibodies) or
             known medical history of acquired immunodeficiency syndrome (AIDS)

          -  Adequate bone marrow function measured within 28 days prior to administration of study
             as defined per protocol.

          -  Adequate rental function as defined per protocol.

          -  Adequate hepatic function as defined per protocol

          -  Women of childbearing potential (WOCBP) patients or male patients who are sexually
             active with WOCBP and female partners of male participants must agree to follow
             instructions of "highly effective methods of contraception) per protocol for duration
             of treatment with study drug(s) plus the specified washout period.

          -  Male participants must be willing to refrain from sperm donation during the study and
             for at least 180 days after the last dose of durvalumab combination therapy, 90 days
             after the last dose of durvalumab or olaparib monotherapy.

        Exclusion Criteria:

          -  Participants with previous brain metastases are eligible provided that they are
             treated, are asymptomatic, and have stable disease at the screening tumor assessment.
             A ≥ 2 week disease stable interval as confirmed by MRI or CT brain w/ contrast (Table
             7.4-2) is required after treatment of brain metastases before initiation of thoracic
             XRT. In addition, subjects must have been either off corticosteroids, or on a stable
             or decreasing dose of ≤10 mg daily prednisone (or equivalent).

          -  Participants who have received prior thoracic XRT are excluded.

          -  Participants with Carcinomatous meningitis

          -  Pregnant or breastfeeding women

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis,
             Wegener syndrome and hypophysitis or uveitis. Patients with an autoimmune
             paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded.
             Patients with type I diabetes mellitus, hypothyroidism only requiring hormone
             replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring
             systemic treatment, or conditions not expected to recur in the absence of an external
             trigger are permitted to enroll

          -  Participants with a condition requiring systemic treatment with either corticosteroids
             (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
             days of study treatment (excluding thoracic radiotherapy). Some exceptions apply.

          -  Prior CPI therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
             antibody (including any other antibody or drug specifically targeting T cell
             co-stimulation or checkpoint pathways). Exception: CPI use with first line
             chemotherapy that is stopped prior to trial enrollment.

          -  Participants who have received any previous treatment with a Poly ADP Ribose
             Polymerase (PARP) inhibitor, including olaparib

          -  Interstitial lung disease (ILD): Any evidence of current ILD or pneumonitis or a prior
             history of ILD or pneumonitis requiring oral or IV glucocorticoids.

          -  Previous malignancies unless a complete control (no evidence of disease) was achieved
             ≥ 2 years prior to study entry AND no additional therapy is required during the study
             period (EXCEPT: adequately treated non-melanoma skin cancer, curatively treated in
             situ cancer and stage 1, grade 1 endometrial cancer).

          -  Participants with a known medical condition that, in the investigator's opinion, would
             increase the risk associated with study participation or study drug(s) administration
             or interfere with the interpretation of safety results.

          -  Major surgery or significant traumatic injury that is not recovered at least 14 days
             before the initiation of thoracic radiation therapy

          -  All toxicities attributed to prior anti-cancer therapy must have been resolved to
             Grade 1 (NCI CTCAE Version 5.0) or baseline before administration of study drug(s).
             Some exceptions apply.

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients.

          -  Patients with known contraindications to radiotherapy, including inherited syndromes
             associated with hypersensitivity to ionizing radiation (e.g., Ataxia-Telangiectasia,
             Nijmegen Breakage Syndrome).

          -  History of allergy or hypersensitivity to any of the study drugs or study drug
             components
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Unacceptable Serious Adverse Events (SAEs)
Time Frame:13 weeks
Safety Issue:
Description:Unacceptable toxicity status at the end of 13-week safety observation period with unacceptable toxicity defined as: Any grade 4 immune related adverse event (irAE), Any ≥ grade 3 noninfectious pneumonitis, Any ≥ grade 3 colitis, Any grade 3 irAE, excluding colitis or pneumonitis, that does not downgrade to grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to ≤ grade 1 or baseline within 14 days, Liver transaminase elevation > 8 × Upper Limit of Normal (ULN) or total bilirubin > 5 × ULN Any ≥ grade 3 non-irAE with exceptions per protocol

Secondary Outcome Measures

Measure:Median Progression Free Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Progression Free Survival (PFS) is defined as the duration from date of registration to date of first documentation of progression assessed by local investigator or symptomatic deterioration (as defined above) or death due to any cause. Patients last known to be alive are censored at date of last contact.
Measure:Overall Survival
Time Frame:Up to 12 months
Safety Issue:
Description:Overall Survival (OS) will is defined as the duration from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • lung cancer

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