nab-Paclitaxel + Gemcitabine for Sarcoma

Recruiting at 15 trial locations

Overseen By Damon Reed, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: CYP2C8/CYP3A4 inhibitors/inducers

Disqualifiers: Pregnancy, HIV, Uncontrolled illness, 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: 3

Duration: 12 months

59 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if the combination of nab-paclitaxel and gemcitabine can stop tumors from growing in patients whose cancer has come back or did not respond to previous treatments. The study also checks if this combination is safe and tolerable. Nab-paclitaxel (Abraxane) is an albumin-bound paclitaxel that has shown clinical activity in advanced breast and lung cancer and has been tested in combination with gemcitabine for advanced pancreatic cancer, improving response rates and survival.

Will I have to stop taking my current medications?

The trial requires that you avoid certain medications that affect the metabolism of paclitaxel, such as ketoconazole, erythromycin, and rifampicin, among others. If you are taking any of these, you would need to stop them to participate in the trial.

What data supports the effectiveness of the drug combination nab-Paclitaxel and Gemcitabine for treating sarcoma?

Research shows that nab-Paclitaxel and Gemcitabine together have been effective in treating pancreatic cancer and have shown promising results in preclinical studies for bone sarcoma, including growth inhibition and improved survival in models of Ewing sarcoma and osteosarcoma. ^{1 2 3 4 5}

Is the combination of nab-Paclitaxel and Gemcitabine generally safe for humans?

The combination of nab-Paclitaxel and Gemcitabine is used as a standard treatment for pancreatic cancer and has been studied for safety in various conditions, including pancreatic cancer and sarcomas. It is generally considered safe, but specific safety data for pediatric sarcoma patients is not yet reported. ^{1 2 3 6 7}

How is the drug nab-Paclitaxel + Gemcitabine unique for treating sarcoma?

The combination of nab-Paclitaxel and Gemcitabine is unique for treating sarcoma because it uses a nanotechnology-based drug (nab-Paclitaxel) that improves drug delivery and effectiveness, showing promising results in preclinical models and offering a potential new option for patients with relapsed or hard-to-treat sarcomas. ^{1 2 3 8 9}

Research Team

Javier Oesterheld, M.D.

Principal Investigator

Carolinas Medical Center, Levine Cancer Institute

Eligibility Criteria

This trial is for young people aged 3 to 30 with certain types of sarcoma, including osteosarcoma and Ewing sarcoma, that have come back or didn't respond to initial treatments. They must have measurable disease, be in good physical condition with a Karnofsky score ≥60, and not pregnant. Participants should not have had prior treatment with the study drugs or recent chemotherapy and agree to use contraception.

Inclusion Criteria

I am between 3 and 30 years old and have been diagnosed with a specific type of sarcoma.

My cancer returned or got worse during my first treatment.

My organs and bone marrow are functioning well.

Exclusion Criteria

I am not taking medications that affect CYP2C8 or CYP3A4 enzymes.

I am not currently taking any cancer treatment medications.

I am allergic to docetaxel or paclitaxel.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nab-Paclitaxel and Gemcitabine on days 1, 8, and 15 of each 28-day cycle, for up to 12 cycles

12 months

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Treatment Details

Interventions

• Gemcitabine
• nab-Paclitaxel

Trial Overview Researchers are testing if nab-Paclitaxel combined with Gemcitabine can stop tumor growth in patients whose sarcomas returned or resisted earlier treatments. The goal is also to see how long patients stay stable without their disease worsening after this treatment combination.

Participant Groups

Group I: Combination Therapy Experimental Treatment 2 Interventions

Participants will receive nab-Paclitaxel and Gemcitabine on days 1, 8, and 15 of each 28 day cycle, for up to 12 cycles.

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

National Pediatric Cancer Foundation

Collaborator

Trials

8

Recruited

300+

Findings from Research

Nab-paclitaxel, a less toxic and more effective drug than docetaxel, showed significant growth inhibition and improved survival in Ewing sarcoma models, suggesting its potential as a treatment option.

The combination of nab-paclitaxel and gemcitabine demonstrated additive effects in osteosarcoma models, supporting further research into this combination for treating bone sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of nanoparticle albumin-bound paclitaxel for treatment of pediatric bone sarcoma. Wagner, LM., Yin, H., Eaves, D., et al.[2015]

In a study of 16 pediatric patients with relapsed/refractory sarcomas, the combination of gemcitabine and nab-paclitaxel was found to be relatively safe, with 55% of treatment cycles resulting in Grade 3 or higher toxicity, primarily hematologic in nature.

The treatment provided clinical benefit to 31% of patients, with a median duration of stable disease of 4.5 months, indicating it may be a viable palliative option for some children with difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas. Metts, JL., Alazraki, AL., Clark, D., et al.[2022]

In a phase II trial involving 11 heavily pretreated patients with relapsed Ewing sarcoma, the combination of gemcitabine and nab-paclitaxel resulted in a confirmed response rate of only 9%, indicating limited efficacy for this treatment in this patient population.

The treatment was associated with significant toxicity, particularly myelosuppression, leading to the removal of 36% of patients due to hematologic issues, despite supportive measures like pegfilgrastim.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of gemcitabine and nab-paclitaxel in patients with recurrent Ewing sarcoma: A report from the National Pediatric Cancer Foundation. Oesterheld, JE., Reed, DR., Setty, BA., et al.[2022]

In a phase I/II study involving 34 Japanese patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine demonstrated a high objective response rate of 58.8%, indicating promising efficacy for this treatment regimen.

The treatment was associated with manageable safety, with the most common severe adverse effects being neutropenia (70.6%) and leukopenia (55.9%), but no treatment-related deaths were reported, suggesting that the regimen can be safely administered with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. Ueno, H., Ikeda, M., Ueno, M., et al.[2022]

References

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

Preclinical evaluation of nanoparticle albumin-bound paclitaxel for treatment of pediatric bone sarcoma. [2015]

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

Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas. [2022]

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

Phase II trial of gemcitabine and nab-paclitaxel in patients with recurrent Ewing sarcoma: A report from the National Pediatric Cancer Foundation. [2022]

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

Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. [2022]

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

Gemcitabine/paclitaxel as first-line treatment of advanced breast cancer. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Prognostic factors for survival with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer in real-life practice: the ANICE-PaC study. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Feasibility of Combination Therapy with Nab-paclitaxel Plus Gemcitabine in Patients with Recurrent Pancreatic Cancer. [2022]

9. France pubmed.ncbi.nlm.nih.gov

The combination of gemcitabine and nab-paclitaxel as a novel effective treatment strategy for undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model. [2022]