Durvalumab in Combination With Chemotherapy in Treating Patients With Advanced Solid Tumors, DURVA+ Trial
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)
About this trial
This phase II trial studies the side effects of durvalumab when given together with chemotherapy in treating patients with solid tumors that have spread to other places in the body (advanced). 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 gemcitabine hydrochloride, pegylated liposomal doxorubicin hydrochloride, capecitabine, carboplatin, paclitaxel, and nab-paclitaxel 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. Giving chemotherapy with durvalumab may improve how immune cells respond and attack tumor cells.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with histologically documented metastatic or locally advanced (not amenable to surgery) solid tumors whose disease has progressed following at least one line of standard therapy and/or no standard of treatment exists that has been shown to prolong survival.
If anti-PD-1 or one of the 6 chemotherapy agents is standard-of-care, prior therapy with the agent would not be required.
Patient must have tumor amenable to biopsy and be willing to undergo a tumor biopsy.
Flash frozen tissue collected as part of another study or from a procedure performed due to medical necessity may be acceptable as the baseline sample if the samples were collected within 3 months prior to registration and the patient has not received any investigational or targeted treatment since that time.
Disqualifiers
Patients who received prior therapy with a checkpoint inhibitor and were taken off drug for serious adverse events are excluded. Patients who had prior CTLA-4 inhibitor treatment and did not experience serious adverse events are eligible for all arms. Patients who had prior PD-L1/PD-1 inhibitor treatment and did not experience serious adverse events are excluded from the durvalumab monotherapy arm but are eligible for the chemotherapy combinations.
Patients with pancreatic cancer, prostate cancer, or microsatellite stable (MSS) colorectal cancer, or other histologies where clinical evidence exists that single-agent inhibition of PD-L1/PD-1 has minimal activity will not receive single-agent durvalumab but may be eligible to receive this agent with chemotherapy (Arms 2-7).
Women who are pregnant or breastfeeding.
Patients who are receiving any other investigational agents. Patients on other trials will be eligible as long as they are no longer receiving study treatment.
Trial design
Design model
Parallel
Treatments tested in this trial
Biopsy Procedure
Procedure/SurgeryUndergo tissue biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Capecitabine
DrugGiven PO
Carboplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT
Durvalumab
Biological/VaccineGiven IV
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Gemcitabine Hydrochloride
DrugGiven IV
Nab-paclitaxel
DrugGiven IV
Paclitaxel
DrugGiven IV
Pegylated Liposomal Doxorubicin Hydrochloride
DrugGiven IV
Treatment groups
115 Participants
are divided into 7 treatment groups7
Treatment groupsSee each treatment group below.
Group A: Arm I (durvalumab)Active comparator 4 interventions
Group B: Arm II (gemcitabine hydrochloride, durvalumab)Experimental treatment 5 interventions
Group C: Arm III (pegylated liposomal doxorubicin, durvalumab)Experimental treatment 6 interventions
Group D: Arm IV (capecitabine, durvalumab)Experimental treatment 5 interventions
Group E: Arm V (carboplatin, durvalumab)Experimental treatment 5 interventions
Group F: Arm VI (paclitaxel, durvalumab)Experimental treatment 5 interventions
Group G: Arm VII (nab-paclitaxel, durvalumab)Experimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Incidence of adverse events
Time frame
Up to 2 cycles (Arms 1-3) or 4 cycles Arms (4-7)Other outcomes
1
Changes in the immune microenvironment
Will assess how these changes alter the pharmacodynamic effects of a checkpoint inhibitor.
Time frame
Baseline up to 3 months after the last dose of study drug2
Immunotherapy response of tumor-infiltrating and circulating T cells
Will investigate whether the response to immunotherapy correlates with patients' genetic aberrations and/or the activation status of tumor-infiltrating and circulating T cells.
Time frame
Up to 3 months after the last dose of study drug3
Immune status of the tumor and overall tumor mutational load
Will explore the relationship between immune status of the tumor and overall tumor mutational load.
Time frame
Up to 3 months after the last dose of study drug4
Cell-free deoxyribonucleic acid (cfDNA)
Will be analyzed by MoCha with the TSO500 targeted sequencing assay (or similar assay) to quantitatively assess longitudinal changes (such as changes in circulating tumor DNA levels as a percentage of total circulating, cell-free DNA) and to identify any mutations that may be associated with study treatment sensitivity or resistance.
Time frame
On day 1 of each treatment cycle and at the time of disease progressionSponsors and contacts
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Source ClinicalTrials.gov