Durvalumab in Combination With Chemotherapy in Treating Patients With Advanced Solid Tumors, (DURVA+ Study)
- Conditions
- Metastatic Malignant Solid NeoplasmLocally Advanced Malignant Solid Neoplasm
- Registration Number
- NCT03907475
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 115
Inclusion Criteria:<br><br> - Patients with histologically documented metastatic or locally advanced (not amenable<br> to surgery) solid tumors whose disease has progressed following at least one line of<br> standard therapy and/or no standard of treatment exists that has been shown to<br> prolong survival.<br><br> - If anti-PD-1 or one of the 6 chemotherapy agents is standard-of-care, prior<br> therapy with the agent would not be required.<br><br> - Patient must have tumor amenable to biopsy and be willing to undergo a tumor biopsy.<br><br> - Flash frozen tissue collected as part of another study or from a procedure<br> performed due to medical necessity may be acceptable as the baseline sample if<br> the samples were collected within 3 months prior to registration and the<br> patient has not received any investigational or targeted treatment since that<br> time.<br><br> - A patient who cannot be safely biopsied may be considered for the study upon<br> discussion with Principal Investigator.<br><br> - Patients must have measurable disease, defined as at least one lesion that can be<br> accurately measured in at least one dimension (longest diameter to be recorded) as<br> >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography<br> (CT) scan.<br><br> - Patients with bone metastases or hypercalcemia on intravenous bisphosphonate<br> treatment, denosumab, or similar agents are eligible to participate and may continue<br> this treatment. Patients with prostate cancer may continue luteinizing<br> hormone-releasing hormone (LHRH) agonists or antagonists.<br><br> - Age = 18 years. Children are excluded from this study, but may be eligible for<br> future pediatric trials<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status =< 2.<br><br> - Absolute neutrophil count >= 1,000/uL (mcL).<br><br> - Platelets >= 100,000/uL (mcL).<br><br> - Total bilirubin < 1.5 x institutional upper limit of normal.<br><br> - This will not apply to patients with confirmed Gilbert syndrome (persistent or<br> recurrent hyperbilirubinemia that is predominantly unconjugated in the absence<br> of hemolysis or hepatic pathology), who will be allowed only at the discretion<br> of the principal investigator (PI), study chair or their designee.<br><br> - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase<br> [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase<br> [SGPT]) =< 3 x institutional upper limit of normal, or up to 5 x upper limit of<br> normal (ULN) if liver metastases are present.<br><br> - Calculated creatinine clearance > 40 mL/min by the Cockcroft-Gault formula<br><br> - Any prior systemic therapy (including checkpoint inhibitors), or major surgery must<br> have been completed >= 3 weeks (> 6 weeks for nitrosoureas or mitomycin C) or 5<br> half-lives of the agent, whichever is shorter, prior to enrollment on protocol, and<br> toxicity from prior treatment must have recovered to eligibility levels. Radiation<br> therapy must have been completed >= 1 week prior to starting treatment.<br> Radiofrequency ablation (RFA) of localized lesions should have been performed >= 1<br> week prior to starting treatment. All radiation-related toxicity must have resolved<br> to < grade 2.<br><br> - Palliative radiotherapy is permitted between disease progression on Arm 1 and<br> crossover to a combination therapy arm (Arms 2-7), provided there is a washout<br> period of >= 1 week and any toxicity from radiation has resolved to < grade 2<br><br> - Patients on any arm may receive palliative radiotherapy or loco-regional<br> ablative therapy and remain on study, provided the radiation is not delivered<br> to the target lesion and the patient does not have tumor progression by<br> Response Evaluation Criteria in Solid Tumors (RECIST)<br><br> - Treatment with systemic immunostimulatory agents (including, but not limited to,<br> interferon-alpha or interleukin-2) must have been completed at least 6 weeks before<br> the first dose of durvalumab.<br><br> - Body weight > 30 kg.<br><br> - Human immunodeficiency virus (HIV)-infected (HIV1/2 antibody-positive) patients may<br> participate if they meet all the following eligibility requirements:<br><br> - They must be on an anti-retroviral regimen with evidence of at least two<br> undetectable viral loads within the past 6 months on this same regimen; the<br> most recent undetectable viral load must be within the past 12 weeks.<br><br> - They must have a CD4 count >= 250 cells/uL over the past 6 months on this same<br> anti-retroviral regimen and must not have had a CD4 count < 200 cells/uL over<br> the past 2 years, unless it was deemed related to chemotherapy-induced bone<br> marrow suppression.<br><br> - For patients who have received chemotherapy in the past 6 months, a CD4<br> count < 250 cells/uL during chemotherapy is permitted as long as viral<br> loads were undetectable during this same chemotherapy.<br><br> - They must have an undetectable viral load and a CD4 count >= 250 cells/uL<br> within 28 days of enrollment.<br><br> - They must not be currently receiving prophylactic therapy for an opportunistic<br> infection and must not have had an opportunistic infection within the past 6<br> months.<br><br> - Monitoring for HIV-infected patients should include:<br><br> - Viral load and CD4 count every 8-10 weeks.<br><br> - The effects of targeted agents on the developing human fetus are unknown. The<br> cytotoxic agents chosen for combination with durvalumab adversely affect human<br> fertility and gestation. For these reasons, women of childbearing potential and men<br> must agree to use highly effective contraception prior to study entry for the<br> duration of study participation and for 6 months following the last dose of a study<br> drug.<br><br> - Because there may be a risk for adverse events in nursing infants secondary to<br> treatment of the mother with these agents, breastfeeding should be discontinued<br> while the patient is on this trial and for 6 months following the last dose of study<br> drug.<br><br> - Patients should be willing not to donate blood while participating in this study or<br> for at least 90 days following the last dose of study drug.<br><br> - Left ventricular ejection fraction greater than 50% or the institutional lower limit<br> of normal by echocardiography (ECHO) at entry (patients enrolling on Arm 3 only).<br><br> - Ability to understand and the willingness to sign a written informed consent<br> document.<br><br>Exclusion Criteria:<br><br> - Patients who received prior therapy with a checkpoint inhibitor and were taken off<br> drug for serious adverse events are excluded. Patients who had prior CTLA-4<br> inhibitor treatment and did not experience serious adverse events are eligible for<br> all arms. Patients who had prior PD-L1/PD-1 inhibitor treatment and did not<br> experience serious adverse events are excluded from the durvalumab monotherapy arm<br> but are eligible for the chemotherapy combinations.<br><br> - Patients with pancreatic cancer, prostate cancer, or microsatellite stable (MSS)<br> colorectal cancer, or other histologies where clinical evidence exists that<br> single-agent inhibition of PD-L1/PD-1 has minimal activity will not receive<br> si
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of adverse events
- Secondary Outcome Measures
Name Time Method