Recruiting
Phase 2

Durvalumab & Chemotherapy

Sponsor:

National Cancer Institute (NCI)

Code:

NCT03907475

Conditions

Locally Advanced Malignant Solid Neoplasm

Metastatic Malignant Solid Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Capecitabine

Carboplatin

Computed Tomography

Study Details

Brief summary:

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.

Conditions

Locally Advanced Malignant Solid Neoplasm

Metastatic Malignant Solid Neoplasm

Study ID

NCT03907475

Start date

Jul 16, 2019

Status verified date

Jul, 2026

Completion date

Jun 1, 2027

Anticipated

Primary completion date

Jun 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.
  • A patient who cannot be safely biopsied may be considered for the study upon discussion with Principal Investigator.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan.
  • Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents are eligible to participate and may continue this treatment. Patients with prostate cancer may continue luteinizing hormone-releasing hormone (LHRH) agonists or antagonists.
  • Age ≥ 18 years. Children are excluded from this study, but may be eligible for future pediatric trials.
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
  • Absolute neutrophil count >= 1,000/uL (mcL).
  • Platelets >= 100,000/uL (mcL).
  • Total bilirubin < 1.5 x institutional upper limit of normal.

  • This will not apply to patients with confirmed Gilbert syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only at the discretion of the principal investigator (PI), study chair or their designee.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =< 3 x institutional upper limit of normal, or up to 5 x upper limit of normal (ULN) if liver metastases are present.
  • Calculated creatinine clearance > 40 mL/min by the Cockcroft-Gault formula
  • Any prior systemic therapy (including checkpoint inhibitors), or major surgery must have been completed >= 3 weeks (> 6 weeks for nitrosoureas or mitomycin C) or 5 half-lives of the agent, whichever is shorter, prior to enrollment on protocol, and toxicity from prior treatment must have recovered to eligibility levels. Radiation therapy must have been completed >= 1 week prior to starting treatment. Radiofrequency ablation (RFA) of localized lesions should have been performed >= 1 week prior to starting treatment. All radiation-related toxicity must have resolved to < grade 2.

  • Palliative radiotherapy is permitted between disease progression on Arm 1 and crossover to a combination therapy arm (Arms 2-7), provided there is a washout period of >= 1 week and any toxicity from radiation has resolved to < grade 2
  • Patients on any arm may receive palliative radiotherapy or loco-regional ablative therapy and remain on study, provided the radiation is not delivered to the target lesion and the patient does not have tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST)
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon-alpha or interleukin-2) must have been completed at least 3 weeks before the first dose of durvalumab.
  • Body weight > 30 kg.
  • Human immunodeficiency virus (HIV)-infected (HIV1/2 antibody-positive) patients may participate if they meet all the following eligibility requirements:

  • They must be on an anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on this same regimen; the most recent undetectable viral load must be within the past 12 weeks.
  • They must have a CD4 count >= 250 cells/uL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/uL over the past 2 years, unless it was deemed related to chemotherapy-induced bone marrow suppression.

  • For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/uL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy.
  • They must have an undetectable viral load and a CD4 count >= 250 cells/uL within 28 days of enrollment.
  • They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months.
  • Monitoring for HIV-infected patients should include:

  • Viral load and CD4 count every 8-10 weeks.
  • The effects of targeted agents on the developing human fetus are unknown. The cytotoxic agents chosen for combination with durvalumab adversely affect human fertility and gestation. For these reasons, women of childbearing potential and men must agree to use highly effective contraception prior to study entry for the duration of study participation and for 6 months following the last dose of a study drug.
  • Because there may be a risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued while the patient is on this trial and for 6 months following the last dose of study drug.
  • Patients should be willing not to donate blood while participating in this study or for at least 90 days following the last dose of study drug.
  • Left ventricular ejection fraction greater than 50% or the institutional lower limit of normal by echocardiography (ECHO) at entry (patients enrolling on Arm 3 only).
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • 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.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions:

  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (e.g. bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. Patients with active tuberculosis (TB) are also excluded.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions:

  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or glucocorticoid equivalent dose of another steroid
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Patients should not be vaccinated with live attenuated vaccines within 30 days before starting or after completing durvalumab treatment.
  • Patients who have a history of seizures will not be eligible, unless they have either not had seizures or have been on stable doses of anti-seizure medicine and had no seizures for 4 weeks, in which case they will be eligible. Patients taking enzyme-inducing anticonvulsants (i.e., carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone) will only be eligible for Arm 1 (durvalumab monotherapy) and Arm 2 (durvalumab + gemcitabine).
  • Patients receiving warfarin are not eligible for Arm 4 (capecitabine) due to the potential for life-threatening interactions. Patients on warfarin are eligible to enroll in one of the other arms provided there is increased vigilance with respect to monitoring international normalized ratio (INR).
  • Patients with uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the past 6 months, invasive fungal infections, or active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e., quantifiable hepatitis B virus \[HBV\]-deoxyribonucleic acid \[DNA\] and/or positive hepatitis B surface antigen \[HbsAg\], quantifiable HCV-ribonucleic acid \[RNA\]), are not eligible to participate. Testing for HBV-DNA and HCV-RNA will be mandatory for patients with hepatocellular carcinoma (HCC) only; testing for hepatitis B or other infections for eligibility will be performed only if clinically indicated.
  • History of grade >= 2 infusion reactions or allergic reactions to humanized monoclonal antibodies. Exception: patients with a history of grade 2 infusion reactions to checkpoint inhibitors may be eligible if resumption of prior therapies with pre-medications has been documented without recurrence of infusion reactions of any grade; those patients should receive the same pre-medications with the first and subsequent doses of durvalumab.
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.

Study Design

Enrollment

115 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Arm I (durvalumab)

Patients receive durvalumab IV over 60 minutes on days 1 and 15 of cycles 1 and 2 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

experimental: Arm II (gemcitabine hydrochloride, durvalumab)

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and durvalumab IV over 60 minutes on days 8 and 22 of cycles 1 and 2 and day 8 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who discontinue gemcitabine hydrochloride continue receiving durvalumab alone as in Arm I. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

experimental: Arm III (pegylated liposomal doxorubicin, durvalumab)

Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 and durvalumab IV over 60 minutes on days 8 and 22 of cycles 1 and 2 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

experimental: Arm IV (capecitabine, durvalumab)

Patients receive capecitabine PO BID on days 1-14, and durvalumab IV over 60 minutes on day 8 of cycle 1, days 1 and 15 of cycle 2, day 8 of cycle 3, and day 1 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

experimental: Arm V (carboplatin, durvalumab)

Patients receive carboplatin IV over 30-60 minutes on day 1 and durvalumab IV over 60 minutes on day 8 of cycle 1, days 1 and 15 of cycle 2, day 8 of cycle 3, and day 1 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

experimental: Arm VI (paclitaxel, durvalumab)

Patients receive paclitaxel IV over 60 minutes on day 1 and durvalumab IV over 60 minutes on day 8 of cycle 1, days 1 and 15 of cycle 2, day 8 of cycle 3, and day 1 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

experimental: Arm VII (nab-paclitaxel, durvalumab)

Patients receive nab-paclitaxel IV over 30 minutes on day 1 and durvalumab IV over 60 minutes on day 8 of cycle 1, days 1 and 15 of cycle 2, day 8 of cycle 3, and day 1 of subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

Interventions

Biopsy Procedure

Undergo tissue biopsy

Biospecimen Collection

Undergo blood sample collection

Capecitabine

Given PO

Carboplatin

Given IV

Computed Tomography

Undergo CT

Durvalumab

Given IV

Echocardiography Test

Undergo ECHO

Gemcitabine Hydrochloride

Given IV

Nab-paclitaxel

Given IV

Paclitaxel

Given IV

Pegylated Liposomal Doxorubicin Hydrochloride

Given IV

Primary outcome measure

  • Incidence of adverse events [ Time Frame: Up to 2 cycles (Arms 1-3) or 4 cycles Arms (4-7) ]

Central Contacts and Locations

Locations

National Cancer Institute Developmental Therapeutics Clinic

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

Site Public Contact

800-411-1222

Principal Investigator:

A P. Chen

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 9, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-09.