NABPLAGEM vs. Nab-Paclitaxel/Gemcitabine for Pancreatic Cancer

(PLATINUM-CAN Trial)

Overseen By Erica S Tsang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University Health Network, Toronto

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Cisplatin, Grade 2 neuropathy, active brain metastases, 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: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different drug combinations to determine which is more effective for treating metastatic pancreatic cancer in individuals with specific BRCA1/2 or PALB2 genetic mutations. One group receives nab-paclitaxel, cisplatin, and gemcitabine, while the other receives nab-paclitaxel and gemcitabine. The trial targets those whose cancer has progressed after first-line treatment with FOLFIRINOX. Individuals with pancreatic cancer and these mutations, whose cancer has worsened after initial treatment, may find this trial suitable. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, contributing to significant advancements in cancer care.

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

You may need to stop taking certain medications. If you are on strong CYP3A4 inhibitors or inducers, you must stop them 14 days before starting the trial.

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

Research has shown that the combination of nab-paclitaxel, cisplatin, and gemcitabine has been studied for its safety in treating certain types of cancer. In a previous study, this combination yielded promising results, with patients living an average of 19.2 months and the cancer not worsening for about 11.8 months. This indicates the treatment was effective for a significant period.

Regarding safety, the treatment is generally well-tolerated, though some patients may experience side effects. Since this combination has been used in studies before, researchers understand how patients might react. Strong evidence from past trials shows that many patients have managed the treatment well.

Side effects can occur, and each person's experience may differ. It's important to discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NABPLAGEM because it combines nab-paclitaxel, cisplatin, and gemcitabine to tackle pancreatic cancer. Unlike standard treatments like nab-paclitaxel with gemcitabine alone, NABPLAGEM introduces cisplatin, which could enhance the treatment's effectiveness by attacking cancer cells in a different way. This combination aims to improve outcomes by using multiple drugs that work together, potentially offering a better response than existing options.

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

This trial will compare two treatment regimens for pancreatic cancer. Research has shown that NABPLAGEM, a combination of nab-paclitaxel, cisplatin, and gemcitabine, can be quite effective. In one study, 71% of patients responded well to this treatment, with some experiencing a complete response. Another study found that patients lived for a median of 16.4 months after receiving this combination. In this trial, one group of participants will receive NABPLAGEM.

Another group will receive nab-paclitaxel with gemcitabine alone, which has shown a median survival of 8.5 months, better than gemcitabine by itself. This suggests that adding cisplatin may enhance treatment effectiveness. Overall, these results provide promising evidence for NABPLAGEM in treating certain pancreatic cancer patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Erica S Tsang, MD

Principal Investigator

Princess Margaret Cancer Centre/University Health Network

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic pancreatic cancer that has a BRCA1/2 or PALB2 mutation, who have already been treated with FOLFIRINOX. Specific details about inclusion and exclusion criteria are not provided.

Inclusion Criteria

My cancer is a type of advanced pancreatic cancer.

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

Not pregnant and not nursing

Exclusion Criteria

I do not have another cancer that could affect this treatment's safety or results.

HIV-infected patients without undetectable viral load

I have hepatitis B or untreated hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either NABPLAGEM or Nab-paclitaxel/Gemcitabine regimen on days 1 and 15 of every cycle

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin

Trial Overview The study compares two chemotherapy regimens: NABPLAGEM (a combination of drugs) versus Nab-Paclitaxel/Gemcitabine in patients whose pancreatic cancer has specific genetic mutations and has progressed after initial treatment.

How Is the Trial Designed?

Group I: Arm 1- NABPLAGEM (Nab-paclitaxel+Cisplatin+Gemcitabine) Experimental Treatment 3 Interventions

Nab-paclitaxel 100 mg/m2 + cisplatin 25 mg/m2 + gemcitabine 800 mg/m2 on days 1 and 15 of every cycle.

Group II: Arm 2 - Nab-paclitaxel+gemcitabine Active Control 2 Interventions

Nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 on days 1 and 15 of every cycle.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Nabpaclitaxel plus S-1 (AS) significantly improved median time to progression (7.1 months) and overall survival (10.2 months) compared to gemcitabine plus S-1 (GS), indicating AS may be a more effective first-line treatment for metastatic pancreatic cancer based on a study of 38 patients.

While both treatments had similar rates of hematological adverse events, AS was associated with a higher risk of sensory neuropathy, suggesting that while AS is effective, it requires careful monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety comparison of nabpaclitaxel plus S-1 and gemcitabine plus S-1 as first-line chemotherapy for metastatic pancreatic cancer. Xu, Y., Guo, X., Fan, Y., et al.[2022]

In a study involving 866 patients with resected pancreatic ductal adenocarcinoma, the combination of nab-paclitaxel and gemcitabine showed a significant improvement in overall survival (OS) compared to gemcitabine alone, with a median OS of 41.8 months versus 37.7 months, respectively.

Although the primary endpoint of disease-free survival (DFS) was not significantly improved with nab-paclitaxel + gemcitabine, the treatment was associated with a higher incidence of grade ≥ 3 adverse events (86% vs. 68% for gemcitabine), indicating a need for careful consideration of safety alongside efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. Tempero, MA., Pelzer, U., O'Reilly, EM., et al.[2023]

In a study of patients with resected pancreatic ductal adenocarcinoma (PDAC), adjuvant chemotherapy with nab-paclitaxel plus gemcitabine (AG) significantly improved median disease-free survival (15.8 months) and overall survival (28.3 months) compared to gemcitabine alone (12.2 months and 20.6 months, respectively).

While AG showed better survival outcomes, it also led to a higher incidence of sensory neuropathy (53.3% in AG vs. 23.3% in GEM), indicating a trade-off between efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. Yin, ZZ., Zhao, ZM., Tang, WB., et al.[2020]

In a study of 200 pancreatic cancer patients receiving gemcitabine and nanoparticle albumin-bound paclitaxel, treatment suspension occurred in 61% of cases, primarily due to severe neutropenia (grade 3/4) in 83.6% of patients.

Low baseline platelet counts and age over 65 were identified as risk factors for treatment suspension, while initiating treatment with a dose reduction helped prevent severe neutropenia and allowed for better management of the chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of risk factors related to administration suspension and severe neutropenia in gemcitabine and nab-paclitaxel treatment. Saito, Y., Takekuma, Y., Kobayashi, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11192994/

Phase II clinical trial of nab‐paclitaxel plus cisplatin plus ... We achieved an ORR of 71% with two CRs, 12‐month OS of 65%, and median survival of 16+ months. The current phase II study was performed to ...

2. ascopubs.org ascopubs.org/doi/10.1200/OA-25-00099

Alliance A022106: A Phase II/III Trial of Nab-Paclitaxel and ... Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality, with a 5-year survival rate of 13%.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1304369

Increased Survival in Pancreatic Cancer with nab ... The median overall survival was 8.5 months in the nab-paclitaxel–gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04605913

Study Details | NCT04605913 | Nab-Paclitaxel + Cisplatin ... This is a Phase I/Ib trial, single-center, non-randomized, open-label study of Protein-bound Paclitaxel, Cisplatin, And Gemcitabine (GCN) Combined with ...

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2752374

Response Rate Following Albumin-Bound Paclitaxel Plus ... The median overall survival was 16.4 months, and the median progression-free survival was 10.1 months. Meaning Adding cisplatin to nab- ...

6. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2730639

Gemcitabine, Cisplatin, and nab-Paclitaxel for the ... Administration of nab-paclitaxel plus gemcitabine-cisplatin resulted in median progression-free survival of 11.8 months and median overall survival of 19.2 ...