Trial Summary
What is the purpose of this trial?This phase I/II trials investigates the side effects of olaparib and durvalumab and how well it works in combination with carboplatin, etoposide, and/or radiation therapy in treating patients with extensive stage-small cell lung cancer (ES-SCLC) who have not received treatment for their disease. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. 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. Chemotherapy drugs, such as carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy sources to kill tumor cells and shrink tumors. Giving olaparib and durvalumab together with carboplatin, etoposide, and/or radiation therapy may help treat patients with ES-SCLC.
Is the drug combination of Carboplatin, Durvalumab, Etoposide, and Olaparib promising for treating small cell lung cancer?Yes, the combination of these drugs shows promise for treating small cell lung cancer. Research suggests that using Olaparib with Durvalumab can be effective, and combining Olaparib with other treatments like Carboplatin has shown positive results in other cancers. This suggests potential benefits for small cell lung cancer as well.138911
What safety data is available for the treatment of Olaparib, Durvalumab, and Chemotherapy/Radiation in Small Cell Lung Cancer?The safety of Olaparib and Carboplatin has been evaluated in a Phase I/Ib study, showing that the combination can be administered safely with common adverse events including nausea, fatigue, and decreased platelet count. The maximum tolerable dose was identified as Olaparib 75 mg BID with Carboplatin AUC 4 mg*min/mL. Durvalumab's safety has been assessed in various solid tumors, indicating it is generally well-tolerated. These studies provide preliminary safety data relevant to the combination treatment in question.126910
What data supports the idea that Olaparib + Durvalumab + Chemotherapy/Radiation for Small Cell Lung Cancer is an effective treatment?The available research shows that combining durvalumab with chemotherapy (platinum-etoposide) significantly improves survival in patients with extensive-stage small-cell lung cancer compared to chemotherapy alone. This is supported by the CASPIAN study, which found that patients receiving durvalumab plus chemotherapy lived longer than those who only received chemotherapy. Although the specific combination of Olaparib + Durvalumab + Chemotherapy/Radiation for small cell lung cancer isn't directly addressed, the success of durvalumab in combination with chemotherapy suggests potential effectiveness when combined with other treatments like olaparib.457911
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop all current medications. However, you cannot use strong or moderate CYP3A inhibitors or inducers, and there are specific washout periods: 2 weeks for CYP3A inhibitors and 3-5 weeks for CYP3A inducers, depending on the drug. Check with the trial team about your specific medications.
Eligibility Criteria
This trial is for adults with extensive-stage small cell lung cancer (ES-SCLC) who haven't had treatment yet. They should have at least one lesion visible on a CT scan, be in good physical condition (ECOG 0-1), weigh over 30 kg, and agree to use two effective forms of contraception if sexually active. People can't join if they've used certain medications recently, have uncontrolled heart conditions or other serious health issues, are pregnant or breastfeeding, or have allergies to the drugs being tested.Inclusion Criteria
My liver enzymes are within the required limits for the trial.
My body weight is over 30 kg.
I am a male and will use a condom and not donate sperm.
I haven't received any systemic therapy for small cell lung cancer.
I am fully active or restricted in physically strenuous activity but can do light work.
My small cell lung cancer is at stage IV, with extensive lung nodules or large tumor volume.
Exclusion Criteria
I am not currently receiving any cancer treatments.
I have been diagnosed with MDS, AML, or have symptoms suggesting these conditions.
I cannot swallow pills or have stomach issues affecting medication absorption.
I have had a bone marrow or double cord blood transplant.
I have heart conditions that are not under control but can be treated.
I have not had major surgery in the last 28 days.
I have brain metastases that have not been treated.
I am allergic to durvalumab, olaparib, or their ingredients.
I have or had inflammatory bowel disease or lung inflammation.
I am not taking strong or moderate drugs that affect enzyme activity.
I had another cancer but was treated successfully over 3 years ago with no signs of it returning.
My cancer is not small cell lung cancer.
I have had an autoimmune disease in the last 2 years.
Treatment Details
The PRIO trial is testing how well patients with ES-SCLC respond to a combination of olaparib and durvalumab along with carboplatin and etoposide chemotherapy and/or radiation therapy. Olaparib inhibits DNA repair in tumor cells while durvalumab helps the immune system attack cancer. The study aims to see if this combo can improve outcomes for these patients.
1Treatment groups
Experimental Treatment
Group I: Treatment (chemo-immunotherapy, radiation therapy)Experimental Treatment5 Interventions
See detailed description.
Carboplatin is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Paraplatin for:
- Ovarian cancer
- Testicular cancer
- Lung cancer
- Head and neck cancer
- Brain cancer
🇪🇺 Approved in European Union as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
🇨🇦 Approved in Canada as Carboplatin for:
- Ovarian cancer
- Small cell lung cancer
- Testicular cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who is running the clinical trial?
M.D. Anderson Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. [2022]Olaparib has single-agent activity against breast/ovarian cancer (BrCa/OvCa) in germline BRCA1 or BRCA2 mutation carriers (gBRCAm). We hypothesized addition of olaparib to carboplatin can be administered safely and yield preliminary clinical activity.
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.
[Efficacy of olaparib combined with pembrolizumab in second-line treatment for extensive-stage small cell lung cancer]. [2020]Objective: To compare the efficacy and safety of olaparib in combination with pembrolizumab with pembrolizumab alone in second-line treatment for patients with extensive stage-small cell lung cancer (ES-SCLC) whose ages ranged from 40 to 80 years. Methods: From March 2017 to October 2019, 21 patients with progressed or relapsed small cell lung cancer after standard first line treatment were enrolled in this study. The olaparib/pembrolizumab group (n=11) was treated by olaparib 300mg twice per day combined with pembrolizumab 200mg once every 3 weeks, while pembrolizumab group was treated by pembrolizumab alone. Results: The objective response rate (ORR) of olaparib/pembrolizumab group and pembrolizumab group were 45.5% and 10.0%, respectively (P=0.149), and the disease control rate (DCR) were 81.8% and 70.0% (P=0.635). The median progression-free survival (PFS) were 5.93 months and 3.53 months (P=0.036), the median overall survival (OS) were 10.43 months and 8.43 months (P=0.063). The adverse reaction incidences of all grades were 90.9% and 70.0% (P=0.311), and the incidences of grade Ⅲ-Ⅴ including myelosuppression were 36.4% and 10.0% (P=0.311), gastrointestinal reaction were 9.1% and 10.0%, (P=1.000) and other immune-related adverse events were 18.2% and 30.0% (P=1.000). Further analysis showed the metastatic number (P=0.006), platinum sensitivity (P=0.036) and LDH level (P=0.022) significantly affected the ORR of olaparib/pembrolizumab therapy. Conclusion: Our preliminary study indicates that olaparib combined with pembrolizumab is an efficient and safe second-line treatment therapy for patients with ES-SCLC.
Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. [2021]In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs).
Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. [2021]First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum-etoposide) showed a significant improvement in overall survival versus platinum-etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum-etoposide versus platinum-etoposide alone.
A Phase I dose-escalation study of two cycles carboplatin-olaparib followed by olaparib monotherapy in patients with advanced cancer. [2021]Preclinical studies have shown synergistic effects when combining PARP1/2 inhibitors and platinum drugs in BRCA1/2 mutated cancer cell models. After a formulation change of olaparib from capsules to tablets, we initiated a dose finding study of olaparib tablets bidaily (BID) continuously with carboplatin to prepare comparative studies in this patient group. Patients were included in a 3 + 3 dose-escalation schedule: olaparib 25 mg BID and carboplatin area under the curve (AUC) 3 mg*min/mL d1/d22, olaparib 25 mg BID and carboplatin AUC 4 mg*min/mL d1/d22, followed by increasing dose-levels of olaparib from 50 mg BID, 75 mg BID, to 100 mg BID with carboplatin at AUC 4 mg*min/mL d1/d22. After two cycles, patients continued olaparib 300 mg BID as monotherapy. Primary objective was to assess the maximum tolerable dose (MTD). Twenty-four patients with a confirmed diagnosis of advanced cancer were included. Most common adverse events were nausea (46%), fatigue (33%) and platelet count decrease (33%). Dose-level 3 (olaparib 75 mg BID and carboplatin AUC 4 mg*min/mL; n = 6) was defined as MTD. Fourteen out of 24 patients (56%) had a partial response as best response (RECIST 1.1). Systemic exposure of the olaparib tablet formulation appeared comparable to the previous capsule formulation with olaparib tablet AUC0-12 of 16.3 μg/mL*h at MTD. Polymers of ADP-ribose levels in peripheral blood mononuclear cells were reduced by 98.7% ± 0.14% at Day 8 compared to Day 1 for dose-level 3. Olaparib tablets 75 mg BID and carboplatin AUC 4 mg*min/mL for two cycles preceding olaparib monotherapy 300 mg is a feasible and tolerable treatment schedule for patients with advanced cancer.
DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]Consolidation durvalumab is standard of care in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) without disease progression following chemoradiotherapy (the 'PACIFIC regimen'). However, many patients with poor performance status, older age or comorbidities may be ineligible for chemotherapy due to expected high toxicity. These patients typically receive radiotherapy alone, with poor survival outcomes. Based on the PACIFIC trial data, and the strong biological rationale for combining radiotherapy with anti-programmed cell death ligand-1 therapy, durvalumab following radiotherapy could provide additional survival benefit versus radiotherapy alone. Here, we describe the DUART trial, a Phase II, open-label, single-arm study assessing the safety and tolerability of durvalumab following radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy (ClinicalTrials.gov Identifier: NCT04249362).
Olaparib and paclitaxel in combination with carboplatin in treatment of ovarian cancer: influence on disease control. [2022]To investigate the efficacy and safety of olaparib and paclitaxel combined with carboplatin in the treatment of ovarian cancer and its impact on disease control.
Rationale and Design of the Phase III KEYLYNK-012 Study of Pembrolizumab and Concurrent Chemoradiotherapy Followed by Pembrolizumab With or Without Olaparib for Stage III Non-Small-Cell Lung Cancer. [2022]Concurrent chemoradiotherapy is a standard therapy for patients with stage III non-small-cell lung cancer (NSCLC). Durvalumab is an approved treatment option following concurrent chemoradiotherapy in the absence of disease progression. The multicenter, phase III, randomized, placebo- and active-controlled, double-blind KEYLYNK-012 study evaluates whether initiation of immunotherapy with pembrolizumab concurrently with chemoradiotherapy, followed by post-chemoradiotherapy pembrolizumab with or without olaparib improves outcomes for participants with stage III NSCLC. (ClinicalTrials.gov: NCT04380636) METHODS: Eligible participants are aged ≥18 years with previously untreated, pathologically confirmed, stages IIIA-C, squamous or nonsquamous NSCLC not suitable for surgery with curative intent. Participants will be randomized 1:1:1 to platinum-doublet chemotherapy plus radiotherapy with pembrolizumab (Groups A and B) or concurrent chemoradiotherapy alone (Group C) for 3 cycles. In the absence of disease progression, participants will receive pembrolizumab plus olaparib placebo (Group A), pembrolizumab plus olaparib (Group B), or durvalumab monotherapy (Group C). Dual primary endpoints are progression-free survival per RECIST version 1.1 by independent central review and overall survival.
New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]Olaparib (Lynparza) is now approved for the adjuvant treatment of adult patients who have, or are suspected to have, the germline variation of BRCA-mutated human epidermal growth factor receptor 2-negative high-risk early breast cancer and who were previously treated with neoadjuvant or adjuvant chemotherapy.
Olaparib and durvalumab in patients with relapsed small cell lung cancer (MEDIOLA): An open-label, multicenter, phase 1/2, basket study. [2023]Preclinical studies have demonstrated increased efficacy with combined DNA damage response inhibition and immune checkpoint blockade compared with either alone. We assessed olaparib in combination with durvalumab in patients with relapsed small cell lung cancer (SCLC).