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

Trial Summary

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.

What data supports the effectiveness of the drug combination Durvalumab + Chemotherapy for Cancer?

Research shows that gemcitabine, a component of this drug combination, is effective for various cancers, including leukemia and carcinoma, and when combined with carboplatin, it has shown improved response and survival rates in non-small-cell lung cancer. ^{1 2 3 4 5}

What makes the drug combination of Durvalumab and chemotherapy unique for cancer treatment?

This treatment combines Durvalumab, an immunotherapy drug that helps the immune system attack cancer cells, with various chemotherapy drugs, offering a potentially more effective approach by targeting cancer through different mechanisms. This combination is unique because it leverages both the immune system and traditional chemotherapy to fight cancer, which may enhance treatment effectiveness compared to using chemotherapy alone. ^{6 7 8 9 10}

What is the purpose of 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.

Research Team

A P Chen

Principal Investigator

National Cancer Institute LAO

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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 8 and 15 of cycle 2, day 8 of cycles 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 8 and 15 of cycle 2, day 8 of cycles 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 8 and 15 of cycle 2, day 8 of cycles 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 orally (PO) twice daily (BID) on days 1-14, and durvalumab IV over 60 minutes on days 8 of cycle 1, day 8 and 15 of cycle 2, day 8 of cycles 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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Gemcitabine plus epirubicin plus taxol (GET) in advanced breast cancer: a phase II study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin combination regimens: importance of dose schedule. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Change in pharmacokinetic and pharmacodynamic behavior of gemcitabine in human tumor xenografts upon entrapment in vesicular phospholipid gels. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

In vitro and in vivo studies of pharmacokinetics and antitumor efficacy of D07001-F4, an oral gemcitabine formulation. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of newer biologics DMARDs in the management of rheumatoid arthritis: A systematic review. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Subcutaneous Methotrexate in Routine Clinical Practice. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Biologic monotherapy in the treatment of rheumatoid arthritis. [2022]