Chemotherapy for Pancreatic Cancer

Recruiting at 320 trial locations

Overseen By Jamie Crawley, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Pregnancy, 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: 5

Duration: Up to 12 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II/III trial compares the effect of the 3-drug chemotherapy combination of nab-paclitaxel, gemcitabine, plus cisplatin versus the 2-drug chemotherapy combination of nab-paclitaxel plus gemcitabine for the treatment of patients with pancreatic cancer that has spread to other places in the body (metastatic) and a known genetic mutation in the BRCA1, BRCA2, or PALB2 gene.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A4 inhibitors or inducers at least 14 days before starting the study treatment. If you're on these medications, you'll need to discontinue them before joining the trial.

What data supports the effectiveness of the drugs used in the chemotherapy for pancreatic cancer trial?

Research shows that gemcitabine combined with nab-paclitaxel improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. Additionally, gemcitabine-taxane combinations have shown survival benefits in metastatic pancreatic cancer. ^{1 2 3 4 5}

What safety data exists for chemotherapy treatments like Gemcitabine, Cisplatin, and Nab-paclitaxel in humans?

Studies have shown that Gemcitabine, Cisplatin, and Nab-paclitaxel are generally well-tolerated in humans, although they can have side effects. It's important for healthcare providers to understand these side effects to help manage them and improve patient care. ^{3 4 6 7 8}

What makes the chemotherapy treatment for pancreatic cancer unique?

This chemotherapy treatment for pancreatic cancer is unique because it combines cisplatin, gemcitabine, and nab-paclitaxel, which are known to be effective in other cancers like ovarian cancer, where paclitaxel is used for platinum-resistant cases. This combination may offer a novel approach by leveraging the strengths of each drug to potentially improve outcomes in pancreatic cancer. ^{9 10 11 12 13}

Eligibility Criteria

This trial is for adults with metastatic pancreatic cancer that has spread and have a BRCA1, BRCA2, or PALB2 gene mutation. They should not have had cisplatin before but may have had gemcitabine and nab-paclitaxel if it was over a year ago. Participants must show disease progression after initial chemotherapy and be recovered from any significant side effects of previous treatments.

Inclusion Criteria

Patients with absolute neutrophil count >= 1,500/mm^3

Patients with total bilirubin =< 2.0 x institutional upper limit of normal

Patients with platelet count >= 100,000/mm^3

Exclusion Criteria

N/A

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive chemotherapy with nab-paclitaxel, gemcitabine, and cisplatin or nab-paclitaxel and gemcitabine on days 1 and 15 of each 28-day cycle

Up to 12 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

Every 3 months for 2 years, then as needed

Treatment Details

Interventions

• Cisplatin
• Gemcitabine
• Nab paclitaxel

Trial Overview The PLATINUM Trial is testing whether adding cisplatin to the standard chemotherapy combo of nab-paclitaxel plus gemcitabine improves outcomes in patients with certain genetic mutations. It's a phase II/III study comparing these two chemo regimens using CT scans, MRI, and biospecimen collection to assess effectiveness.

Participant Groups

Group I: Arm I (nab-paclitaxel, gemcitabine, cisplatin) Experimental Treatment 6 Interventions

Patients receive nab-paclitaxel IV over 30-40 minutes, gemcitabine IV over 30-40 minutes, and cisplatin IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study.

Group II: Arm II (nab-paclitaxel, gemcitabine) Active Control 5 Interventions

Patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

In a study of 58 patients with resectable metastatic pancreatic cancer treated with gemcitabine and docetaxel, the median overall survival was 52 months, with a 5-year survival rate of 49%, indicating a favorable outcome for this treatment approach.

The study found that while 52% of patients experienced significant toxicity (grade 3 or 4), the majority completed their treatment regimen, and the use of chemoradiation after gem/tax was positively associated with improved survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival? Kanji, ZS., Edwards, AM., Mandelson, MT., et al.[2022]

In a study of 80 Italian patients with metastatic pancreatic cancer, treatment with nab-paclitaxel in combination with gemcitabine resulted in a median overall survival of 8 months and a median progression-free survival of 5 months, indicating its efficacy.

Nab-paclitaxel was well-tolerated and led to significant pain relief, with reductions in the tumor marker CA 19-9 correlating positively with overall survival, suggesting it may be a useful predictor of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. De Luca, R., Blasi, L., Alù, M., et al.[2022]

Recent treatment regimens for advanced pancreatic cancer, including gemcitabine, FOLFIRINOX, and nab-paclitaxel, have shown varying levels of efficacy, highlighting the importance of understanding their unique safety profiles.

Nurses play a crucial role in patient education and symptom management, as each treatment regimen has different adverse events that need to be identified and managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. Hronek, JW., Reed, M.[2017]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a phase II study involving 45 patients with advanced pancreatic cancer, the combination of gemcitabine and cisplatin resulted in a low overall response rate of only 9%, with one complete and four partial responses observed.

Despite some patients experiencing stable disease (46%) and a median survival of 5.6 months, the study concluded that this chemotherapy regimen did not provide a significant advantage in efficacy, and side effects were primarily hematological, with notable toxicities requiring dose reductions in 31% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Cascinu, S., Labianca, R., Catalano, V., et al.[2022]

In a phase III clinical trial involving 42 patients with locally advanced or metastatic pancreatic cancer, both gemcitabine (GEM) alone and GEM combined with cisplatin (CDDP) showed moderate efficacy, with overall response rates of 31.3% for GEM and 27.8% for the combination therapy.

The study demonstrated that GEM or GEM plus CDDP improved the quality of life and prolonged survival times, with 6-month survival rates of 81.3% for GEM and 61.6% for GEM plus CDDP, while maintaining a manageable toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine or gemcitabine plus cisplatin for in 42 patients with locally advanced or metastatic pancreatic cancer. Wang, X., Ni, Q., Jin, M., 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]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

The metal complex CTDP demonstrated comparable antitumor activity to cisplatin (DDP) in a sensitive ovarian tumor line, showing significant colony growth reduction at various concentrations, while also exhibiting a potentially better safety profile due to lower toxicity.

The ruthenium complex ICR was the most effective compound against the DDP-resistant ovarian tumor line, outperforming DDP, indicating its potential as a promising treatment option for resistant ovarian cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro evaluation of platinum, titanium and ruthenium metal complexes in cisplatin-sensitive and -resistant rat ovarian tumors. Frühauf, S., Zeller, WJ.[2019]

In a phase II study involving 55 patients with advanced adenocarcinoma of the upper gastrointestinal tract, cis-diaminodichloroplatinum (II) (cis-DDP) showed minimal efficacy, with only 3 partial responses (6%) among 51 evaluable patients.

The treatment was associated with moderate toxicity, primarily cumulative nephrotoxicity, and myelosuppression occurred in 25% of patients, particularly those who had previously received other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diaminodichloroplatinum (II) chemotherapy for advanced adenocarcinoma of the upper gastrointestinal tract. Kantarjian, H., Ajani, JA., Karlin, DA.[2018]

The cationic monofunctional platinum(II) complex, cDPCP, shows significant anticancer activity in mouse models and is effectively taken up by organic cation transporters that are prevalent in human colorectal cancers.

cDPCP binds to DNA in a unique way that blocks transcription, and while its DNA adducts are repaired less efficiently than those of traditional platinum drugs, its distinct properties suggest it could be a promising treatment option for cancers that express the relevant transporters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects. Lovejoy, KS., Todd, RC., Zhang, S., et al.[2021]

In a study involving 12 patients with advanced ovarian adenocarcinoma, an alternating chemotherapy regimen of cis-platin (DDP) and high-dose methotrexate plus cyclophosphamide (Mecy) demonstrated significant effectiveness as a salvage treatment.

The regimen consisted of four weekly doses of DDP followed by monthly courses of Mecy, indicating a promising approach for patients who may not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-platin-Mecy as salvage chemotherapy in recurrent advanced ovarian carcinoma. Belli, M., Colantuoni, G., Di Iorio, B.[2013]

References

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

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]

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

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival? [2022]

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

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer. [2022]

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

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. [2017]

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

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). [2022]

7. China pubmed.ncbi.nlm.nih.gov

Gemcitabine or gemcitabine plus cisplatin for in 42 patients with locally advanced or metastatic pancreatic cancer. [2022]

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

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. [2023]

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

Treatment of ovarian cancer: current status. [2015]

10. Germany pubmed.ncbi.nlm.nih.gov

In vitro evaluation of platinum, titanium and ruthenium metal complexes in cisplatin-sensitive and -resistant rat ovarian tumors. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Cis-diaminodichloroplatinum (II) chemotherapy for advanced adenocarcinoma of the upper gastrointestinal tract. [2018]

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

cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects. [2021]

13. Italy pubmed.ncbi.nlm.nih.gov

Cis-platin-Mecy as salvage chemotherapy in recurrent advanced ovarian carcinoma. [2013]