Durvalumab + Chemotherapy for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Enzyme-inducing anticonvulsants

Disqualifiers: Autoimmune disorders, Active infections, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Variable (21 or 28 days per cycle)

115 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of durvalumab combined with various chemotherapy drugs in treating advanced solid tumors that have spread. Durvalumab, an immunotherapy, helps the immune system attack cancer cells, while chemotherapy kills or stops their growth. The trial includes several groups testing different combinations of durvalumab with chemotherapy drugs. It is suitable for patients whose cancer has progressed despite previous treatments and who have tumors that can be biopsied. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people, offering patients a chance to benefit from promising new therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like immunosuppressive drugs and enzyme-inducing anticonvulsants may affect eligibility or require adjustments. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that durvalumab is generally safe for patients with various types of cancer. Most people tolerate it well, though some may experience uncommon side effects like pneumonia and heart problems. When combined with nab-paclitaxel, no new safety issues emerged, indicating no unexpected side effects.

Research on the combination of paclitaxel and durvalumab indicates it is safe, with no severe side effects limiting the dosage. Similarly, combining carboplatin and durvalumab mostly resulted in mild side effects, with only a few serious cases like anemia.

The pairing of gemcitabine and durvalumab has been used safely in other studies, though some risks of serious reactions exist, as with other combinations. The combination of pegylated liposomal doxorubicin and durvalumab is generally well-tolerated, though concerns about heart-related side effects remain.

Lastly, the combination of capecitabine and durvalumab has not shown any unexpected side effects, suggesting it is generally safe for patients.

Since this trial is in Phase 2, the treatment has already been tested in smaller groups, providing some evidence of its safety, though more information is still being collected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine durvalumab, a checkpoint inhibitor, with various chemotherapy agents to potentially enhance immune system response against cancer. Unlike the standard of care that often relies on single-agent chemotherapy, these combinations aim to boost the body's natural defenses by blocking the PD-L1 pathway, potentially leading to better outcomes. Each treatment arm pairs durvalumab with different agents like nab-paclitaxel or carboplatin, offering varied mechanisms of action that could target cancer cells more effectively. This approach might not only improve the efficacy of cancer treatment but also reduce side effects compared to traditional chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

Research has shown that durvalumab, a type of immunotherapy, can help treat various cancers. For instance, patients with certain lung cancers who took durvalumab lived longer than those who did not. In this trial, participants may receive durvalumab with different chemotherapies. For example, when combined with nab-paclitaxel, some patients experienced tumor shrinkage or halted growth. The combination of paclitaxel and durvalumab appears promising for treating metastatic breast cancer. Durvalumab with carboplatin has been well-tolerated and shown good results, especially as an initial treatment. Studies have found that combining gemcitabine with durvalumab can improve survival rates. When used with pegylated liposomal doxorubicin, durvalumab helped stabilize tumors in many patients. Combining capecitabine with durvalumab led to a high number of patients responding well, demonstrating the treatment's potential to shrink or control tumor growth. ^{2 6 7 8 9}

Who Is on the Research Team?

A P Chen

Principal Investigator

National Cancer Institute LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have spread and are not responding to standard treatments. Participants must be willing to undergo a biopsy, have an ECOG performance status of 0-2 (able to perform daily activities), adequate organ function, no serious autoimmune or inflammatory disorders, and not pregnant or breastfeeding. They should agree to use effective contraception and cannot have had certain severe reactions to similar drugs.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document

I am willing to have a biopsy of my tumor.

I have bone metastases or high calcium levels and am on specific treatments but can still participate.

Exclusion Criteria

I am not taking warfarin, so I can participate in the capecitabine part of the study.

You currently have or have had an autoimmune or inflammatory disorder, unless it meets certain exceptions.

You have had a transplant using an organ from another person.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive durvalumab in combination with chemotherapy. Treatment cycles repeat every 21 or 28 days depending on the arm, in the absence of disease progression or unacceptable toxicity.

Variable (21 or 28 days per cycle)

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes monthly visits for 3 months.

3 months

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Carboplatin
• Durvalumab
• Gemcitabine Hydrochloride
• Nab-paclitaxel
• Paclitaxel
• Pegylated Liposomal Doxorubicin Hydrochloride

Trial Overview The DURVA+ study is testing the effectiveness of Durvalumab combined with various chemotherapy drugs like gemcitabine hydrochloride, pegylated liposomal doxorubicin hydrochloride, capecitabine, carboplatin, paclitaxel, and nab-paclitaxel in treating patients whose cancer has spread significantly. The goal is to see if this combination helps the immune system better attack cancer cells.

How Is the Trial Designed?

Group I: Arm VII (nab-paclitaxel, durvalumab) Experimental Treatment 5 Interventions

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.

Group II: Arm VI (paclitaxel, durvalumab) Experimental Treatment 5 Interventions

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.

Group III: Arm V (carboplatin, durvalumab) Experimental Treatment 5 Interventions

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.

Group IV: Arm IV (capecitabine, durvalumab) Experimental Treatment 5 Interventions

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.

Group V: Arm III (pegylated liposomal doxorubicin, durvalumab) Experimental Treatment 6 Interventions

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.

Group VI: Arm II (gemcitabine hydrochloride, durvalumab) Experimental Treatment 5 Interventions

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.

Group VII: Arm I (durvalumab) Active Control 4 Interventions

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.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of gemcitabine, epirubicin, and taxol (GET) showed a high overall response rate of 92% in 36 patients with metastatic breast cancer, indicating its potential effectiveness as a front-line treatment.

Despite some significant side effects, including grade 4 neutropenia in 64% of patients, the GET regimen was well tolerated, leading to promising progression-free survival of 21 months and warranting further investigation in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus epirubicin plus taxol (GET) in advanced breast cancer: a phase II study. Conte, PF., Gennari, A., Donati, S., et al.[2022]

Disease-modifying antirheumatic drugs (DMARDs) are essential for treating immune-mediated inflammatory diseases (IMIDs), but they carry a risk of malignancy, which is a significant concern for patients, especially since many IMIDs already have a higher background risk of cancer.

Some conventional synthetic DMARDs, like chloroquine, hydroxychloroquine, and methotrexate, have shown potential antineoplastic properties, suggesting they could be beneficial for patients with both IMIDs and existing malignancies, which may help guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review. Hsieh, CH., Huang, YW., Tsai, TF.[2022]

Combining gemcitabine with carboplatin has shown improved response and survival rates in patients with advanced non-small-cell lung cancer compared to older platinum-based treatments.

Carboplatin, due to its lower nonhematologic toxicities, has allowed for the development of new combination therapies that enhance the efficacy and tolerability of cancer treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin combination regimens: importance of dose schedule. Gandara, DR., Lau, DH., Lara, PN., et al.[2022]

D07001-F4, a new oral formulation of gemcitabine, demonstrated a 34% oral bioavailability, significantly improving upon the poor oral absorption of traditional gemcitabine.

In both in vitro and in vivo studies, D07001-F4 showed enhanced antitumor activity against multiple cancer cell lines and xenograft models compared to standard gemcitabine hydrochloride, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo studies of pharmacokinetics and antitumor efficacy of D07001-F4, an oral gemcitabine formulation. Hao, WH., Wang, JJ., Hsueh, SP., et al.[2022]

Methotrexate (MTX) is the most commonly used drug in combination therapies for rheumatoid arthritis, showing the best results when paired with leflunomide, cyclosporine, or in a triple combination with sulphasalazine and hydroxychloroquine.

Combining MTX with biologics, especially TNF inhibitors, abatacept, rituximab, or tocilizumab, enhances treatment efficacy and helps prevent disease progression, with safety profiles similar to individual medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination therapy using methotrexate with DMARDs or biologics--current status]. Krüger, K.[2021]

Covalent gemcitabine immunochemotherapeutics, designed to target specific cancer cell receptors (EGFR and HER2/neu), show enhanced anti-cancer potency against resistant mammary adenocarcinoma cells, indicating a promising strategy for improving chemotherapy effectiveness.

The dual targeting approach not only increases the cytotoxic effects of gemcitabine but also potentially prolongs its plasma half-life and reduces side effects on healthy tissues, making it a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine. Coyne, CP., Jones, T., Bear, R.[2020]

The new liposomal formulation of gemcitabine (GemLip) demonstrated significantly higher antitumor activity compared to the conventional formulation (GemConv), achieving complete tumor remissions in 7 out of 8 mice at a lower dose (6 mg/kg) in a human soft tissue sarcoma model.

GemLip showed a 35-fold higher plasma concentration and a much longer serum half-life (13.3 hours) compared to GemConv (0.15 hours), indicating better pharmacokinetics and sustained drug release, which likely contributes to its enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Change in pharmacokinetic and pharmacodynamic behavior of gemcitabine in human tumor xenografts upon entrapment in vesicular phospholipid gels. Moog, R., Burger, AM., Brandl, M., et al.[2022]

In a study of 8,394 patients, subcutaneous (SC) methotrexate (MTX) showed higher continuation rates compared to oral MTX, with a rate ratio of 1.54, indicating better tolerance and adherence to treatment.

SC MTX was associated with significantly fewer adverse events compared to biologic and combination therapies, suggesting it is a safer option in routine clinical practice, despite being administered at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Subcutaneous Methotrexate in Routine Clinical Practice. Li, CKH., Baker, K., Jones, T., et al.[2022]

A systematic review of phase 3 clinical trials involving biologic DMARDs (Adalimumab, Baricitinib, Pefacitinib, and Sirukumab) showed significant improvements in the ACR 20 response rate for these newer agents, with rates of 72.4% for SB5, 70% for Baricitinib, and up to 74.5% for Pefacitinib at various time points.

The study indicates that these newer biologics not only improve rheumatoid arthritis symptoms effectively but also maintain an acceptable safety profile compared to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of newer biologics DMARDs in the management of rheumatoid arthritis: A systematic review. Zago, BA., Priyadharshini, A., Vijayakumar, TM.[2022]

Biologics, especially when combined with methotrexate (MTX), are recommended for treating rheumatic diseases, but many patients experience intolerances that negatively impact their quality of life.

In practice, about 30% of patients receiving biological therapy do not use a concomitant DMARD, highlighting a gap between clinical recommendations and real-world treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic monotherapy in the treatment of rheumatoid arthritis. Detert, J., Klaus, P.[2022]

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