Chemotherapy Combination for Pancreatic Cancer

No longer recruiting at 28 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Immunosuppressants, PD1 inhibitors

Disqualifiers: Other malignancies, Autoimmune disorders, Cardiac dysfunction, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: Until progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for treating pancreatic cancer that has spread. Researchers aim to determine if adding two new immunotherapy drugs, durvalumab and tremelimumab, to the usual chemotherapy drugs, gemcitabine and nab-paclitaxel, can improve treatment outcomes. Suitable participants include those with metastatic pancreatic cancer who have not yet received treatment for this advanced stage. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot have used immunosuppressive medications within 28 days before starting the study, except for certain corticosteroids. 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?

Research has shown that the combination of gemcitabine, nab-paclitaxel, durvalumab, and tremelimumab is generally well-tolerated. Studies have not identified any major safety concerns when these drugs are used together. In patients with advanced cancer, adding durvalumab and tremelimumab did not cause unexpected side effects. These treatments proved safe for patients who had not previously received chemotherapy. While side effects can occur with any treatment, the data so far suggests that this combination does not present significant safety issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the new combination treatment of gemcitabine, nab-paclitaxel, durvalumab, and tremelimumab for pancreatic cancer because it brings immunotherapy into the mix. Unlike standard chemotherapy options, which focus on directly attacking cancer cells, durvalumab and tremelimumab are immunotherapy drugs that work by boosting the body's own immune system to fight cancer. Durvalumab blocks the PD-L1 protein, helping immune cells recognize and attack cancer cells, while tremelimumab targets the CTLA-4 protein to further enhance immune response. By combining these immunotherapies with traditional chemotherapy agents, this treatment aims to create a more powerful and comprehensive approach against pancreatic cancer.

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

Research shows that combining gemcitabine and nab-paclitaxel can extend the lives of pancreatic cancer patients. One study found that 35% of patients using this combination survived after one year, compared to 22% using only gemcitabine. In this trial, one group will receive gemcitabine and nab-paclitaxel, while another group will receive these drugs along with durvalumab and tremelimumab. Although previous studies have not demonstrated clear benefits from adding durvalumab and tremelimumab, some research suggests this combination might benefit patients with specific genetic markers, such as ATM mutations. In animal studies, using durvalumab and tremelimumab together shrank tumors more effectively than when used alone. ^{1 2 6 7 8}

Who Is on the Research Team?

Derek Jonker

Principal Investigator

Ottawa Hospital Research Institute, ON Canada

Are You a Good Fit for This Trial?

This trial is for adults with metastatic pancreatic ductal adenocarcinoma who haven't had treatment for their advanced disease. They must have measurable disease, be in good health otherwise, and not have used certain drugs before. Participants need to provide tissue and blood samples, complete quality of life questionnaires, use effective contraception if childbearing potential exists, and be able to follow the trial procedures.

Inclusion Criteria

Must have presence of measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit within 4 weeks of randomization to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue of adequate amount and quality in order that the specific correlative marker assays proscribed in the protocol may be conducted.

Patient must consent to provision of samples of blood, serum and plasma in order that the specific correlative marker assays proscribed may be conducted.

Exclusion Criteria

active bleeding diatheses;

Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.

Patients with alopecia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Gemcitabine and Nab-Paclitaxel, with or without Durvalumab and Tremelimumab, until progression or unacceptable toxicity

Until progression or unacceptable toxicity

Days 1, 8, 15 every 28 days

Follow-up

Participants are monitored for overall survival and progression-free survival

35 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Gemcitabine
• Nab-paclitaxel
• Tremelimumab

Trial Overview The study compares standard chemotherapy (gemcitabine and nab-paclitaxel) against a combination that adds two immunotherapy drugs (durvalumab and tremelimumab). The goal is to see if adding these immune-targeting drugs can better treat this type of cancer compared to the usual approach.

How Is the Trial Designed?

Group I: Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab Experimental Treatment 4 Interventions

Gemcitabine 1000 mg/m2 IV \& Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 15 Q28 days. plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity.

Group II: Gemcitabine plus Nab-Paclitaxel Active Control 2 Interventions

Gemcitabine 1000 mg/m2 IV \& Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days.

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

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. nature.com nature.com/articles/s41467-022-32591-8

The CCTG PA.7 phase II trial of gemcitabine and nab- ... In conclusion, the CCTG PA. 7 trial did not demonstrate a benefit from adding durvalumab and tremelimumab to gemcitabine and nab-paclitaxel as ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02879318

NCT02879318 | Gemcitabine and Nab-Paclitaxel vs ... Combination of durvalumab and tremelimumab have also been studied and when combined have been shown to increase tumour shrinkage in animals compared to either ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10631439/

Systemic treatment for advanced pancreatic cancer - PMC The nab-paclitaxel-gemcitabine group had a survival rate of 35% at one year compared to 22% in the gemcitabine alone group and 9% compared to 4% at two years.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.4135

Predictive value of germline ATM mutations in the CCTG ... GEM, Nab-P, D+T was associated with improved OS in patients with ATM mutations (HR 0.10, 90% CI 0.03-0.37; median OS 13.9 months vs. 4.9 months) ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589004225013975

Evaluating cadonilimab efficacy and safety in retrospective ... The results indicated that the addition of cadonilimab was associated with an improved median progression-free survival compared to chemotherapy ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.4_suppl.349

The Canadian Cancer Trials Group PA.7 trial This randomized phase II study (ClinicalTrials.gov NCT02879318) is assessing the efficacy and safety of GEM and Nab-P vs. GEM, Nab-P, D, and T in patients (pts ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804920313137

Triplet combination of durvalumab, tremelimumab, and ... There have been no reported safety concerns with the use of the gemcitabine and nab-paclitaxel in combination with durvalumab (anti-PD-L1 IgG1, fully-human mAb ...

8. ccanewsonline.com ccanewsonline.com/web-exclusives/phase-2-study-assessing-tolerability-efficacy-and-biomarkers-for-durvalumab-tremelimumab-and-gemcitabine-cisplatin-in-chemo-naive-advanced-btc

Phase 2 Study Assessing Tolerability, Efficacy, and ... Durvalumab ± tremelimumab plus chemotherapy was well-tolerated and showed promising efficacy in chemotherapy-naïve patients with advanced biliary tract ...