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Clinical Trial 19942

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT03923270

Phase: Phase I
Principal Investigator: Chiappori, Alberto

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study 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

Summary

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).

Objective

The safety lead-in phase I is to confirm the recommended phase II dose of durvalumab combinations (arms B and C) among patients treated with thoracic XRT (30 Gy in 10 fractions) following standard chemotherapy (4-6 cycles of platinum-based chemotherapy). Part 2: Phase IB is to evaluate the safety of durvalumab monotherapy and/or combinations with thoracic XRT after standard chemotherapy and to determine the preliminary activity of durvalumab monotherapy and/or combinations with thoracic XRT after standard treatment chemotherapy using 6 months PFS rate as surrogate endpoint. Secondary Objectives: To estimate the median PFS among patients treated with durvalumab monotherapy and/or combinations with thoracic XRT after standard chemotherapy. To estimate the median OS and 1-year OS rate among patients treated with durvalumab monotherapy and/or combinations with thoracic XRT after standard chemotherapy. Exploratory Objectives: To perform rigorous evaluation of (potential) predictive and/or prognostic biomarkers in peripheral blood. To bank and store available formalin-fixed, paraffin-embedded (FFPE) diagnostic tumor biopsy specimens to perform future (potential) predictive and/or prognostic biomarker studies.

Treatments

Therapies

Immunotherapy; Therapy (NOS)

Medications

AMP-514 (Durvalumab); CP-675,206 (tremelimumab); Durvalumab (); MEDI4736 (Durvalumab); Olaparib (Lynparza); tremelimumab ()

Inclusion Criteria

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).

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. Participants 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

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