Gemcitabine + Nab-paclitaxel + IM156 for Pancreatic Cancer

Overseen By Shubham Pant, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Biguanides, CYP2D6 substrates

Disqualifiers: Diabetes, Serious infections, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if adding a new medication, IM156, to treatment with gemcitabine and nab-paclitaxel is safe and tolerable. The ability of this combination to improve the success of this treatment for these patients will also be studied.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications, specifically those that are sensitive CYP2D6 substrates and biguanides like metformin. If you are on these medications, you would need to stop them to participate in the trial.

What data supports the effectiveness of the drug combination Gemcitabine, Nab-paclitaxel, and IM156 for pancreatic cancer?

Research shows that combining Gemcitabine and Nab-paclitaxel improves survival rates and tumor response in patients with advanced pancreatic cancer compared to using Gemcitabine alone. ^{1 2 3 4 5}

Is the combination of Gemcitabine, Nab-paclitaxel, and IM156 safe for humans?

The combination of Gemcitabine and Nab-paclitaxel has been studied for pancreatic cancer, showing some side effects like peripheral neuropathy (nerve damage causing pain or numbness) and myelotoxicity (bone marrow suppression). Rare cases of congestive heart failure (a condition where the heart can't pump blood effectively) have also been reported. ^{6 7 8 9 10}

What makes the drug Gemcitabine + Nab-paclitaxel + IM156 unique for pancreatic cancer?

This drug combination is unique because it includes IM156, which is not typically part of standard treatments for pancreatic cancer. The addition of IM156 may offer a new approach to enhance the effectiveness of the existing combination of Gemcitabine and Nab-paclitaxel, which is already known to improve survival rates compared to Gemcitabine alone. ^{1 3 5 11 12}

Research Team

Shubham Pant, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced pancreatic cancer who haven't had treatment for metastatic disease. They must understand the study and agree to sign a consent form, have measurable disease, possibly be HIV-positive but with undetectable viral load, not be on certain medications or have serious health issues that could affect safety or compliance.

Inclusion Criteria

Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

I am 18 years old or older.

I finished any previous cancer treatments at least 6 months ago.

Exclusion Criteria

Patients with uncontrolled underlying medical conditions

Pregnant or breastfeeding women are excluded

Patients with a history of alcohol or drug abuse within 12 weeks prior to screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Identify the recommended phase 2 dose (RP2D) of IM156 in combination with gemcitabine and nab-paclitaxel

8-12 weeks

Dose Expansion

Evaluate IM156 at the RP2D with gemcitabine and nab-paclitaxel

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemcitabine
• IM156
• Nab paclitaxel

Trial Overview The study tests if IM156 added to gemcitabine and nab-paclitaxel is safe and improves treatment outcomes in patients with advanced pancreatic cancer. It's an early-phase trial to assess this combination's tolerability and potential effectiveness.

Participant Groups

Group I: Dose Escalation Phase followed by a Dose Expansion Phase Experimental Treatment 3 Interventions

In the Dose Escalation Phase of the study, we will identify the RPD2 of IM156. Subsequently, we will evaluate IM156 at the RP2D (established in the Dose Expansion Phase) and gemcitabine + nab-paclitaxel in the Dose Expansion Phase.

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 12 patients with elevated bilirubin levels, the combination of gemcitabine (GEM) and nab-paclitaxel (NabP) showed a median overall survival of 13.9 months, indicating improved efficacy compared to previous findings with GEM alone.

The treatment was found to be safe, with no admissions related to toxicity, and a disease control rate of 58%, suggesting that GEM-NabP can be effectively administered to patients who were previously excluded from studies due to hyperbilirubinemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-modified gemcitabine plus nab-paclitaxel front-line in advanced pancreatic ductal adenocarcinoma with baseline hyperbilirubinemia. Rogers, JE., Mizrahi, JD., Shroff, RT., et al.[2022]

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 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]

In a study of 27 patients with unresectable pancreatic cancer, nab paclitaxel plus gemcitabine was found to be effective and well-tolerated in elderly patients aged 75 and older, showing similar disease control rates and overall survival compared to younger patients.

Despite a lower relative dose intensity of the drugs in the elderly group, the safety profile was comparable, with neutropenia being the most common severe adverse event, indicating that this treatment regimen can be safely administered to older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients. Ishimoto, U., Kinoshita, A., Hirose, 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]

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

In a phase II trial involving 61 patients with borderline resectable pancreatic cancer, the neoadjuvant therapy of nab-paclitaxel plus gemcitabine resulted in a median overall survival of 25.2 months and a median recurrence-free survival of 12.3 months, indicating promising efficacy.

The treatment had a high resection rate of 73.8% and an R0 resection rate of 63.9%, but it also presented significant safety concerns, with 73.8% of patients experiencing grade 3/4 adverse events, highlighting the need for careful patient selection, especially for those with prior lung issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial). Okada, KI., Kimura, K., Yamashita, YI., et al.[2023]

References

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

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China. [2020]

2. China pubmed.ncbi.nlm.nih.gov

Dose-modified gemcitabine plus nab-paclitaxel front-line in advanced pancreatic ductal adenocarcinoma with baseline hyperbilirubinemia. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma. [2023]

6. Greece pubmed.ncbi.nlm.nih.gov

Congestive heart failure secondary to gemcitabine nab-paclitaxel in patients with pancreatic cancer. [2022]

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

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

8. Germany pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients. [2022]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

First-line gemcitabine plus nab-paclitaxel for elderly patients with metastatic pancreatic cancer: Crossing the frontier of age? [2022]

11. Greece pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial). [2023]