nab-Paclitaxel + Gemcitabine for Sarcoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining nab-paclitaxel (a type of chemotherapy) and gemcitabine (also known as Gemzar, another chemotherapy drug) can stop or slow tumor growth in individuals with certain sarcomas, including osteosarcoma and Ewing sarcoma, that have recurred or resisted other treatments. The trial also evaluates how long the disease remains stable and assesses the treatment's safety for patients. Individuals whose tumors have returned or worsened after initial treatments, and who have specific types of sarcoma measurable on scans, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that nab-Paclitaxel combined with Gemcitabine is likely to be safe for humans?

Research has shown that using nab-paclitaxel and gemcitabine together is generally safe for treating various types of sarcoma, a kind of cancer. In one study with 16 children whose sarcomas had returned or didn't respond to other treatments, this combination was well-tolerated, meaning most children could handle it without major problems.

Another study found that this drug pair caused low toxicity, or few harmful side effects, in patients with soft tissue sarcomas. This suggests that the treatment usually doesn't lead to severe side effects. While some risk always exists, evidence indicates that most patients can manage this treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about nab-Paclitaxel and Gemcitabine for treating sarcoma because this combination offers a unique approach compared to standard options. Nab-Paclitaxel is an innovative formulation of paclitaxel that uses albumin-bound nanoparticles, which may improve drug delivery to the tumor and increase effectiveness. Gemcitabine works by interfering with DNA replication, making the combination potentially more powerful by attacking the cancer cells in multiple ways. This dual approach could potentially lead to better outcomes for patients with sarcoma, a condition that often has limited effective treatment options.

What evidence suggests that nab-paclitaxel combined with gemcitabine might be an effective treatment for sarcoma?

Research has shown that a combination of two drugs, nab-paclitaxel and gemcitabine, effectively treats certain cancers. In studies with pancreatic cancer patients, those receiving both drugs lived longer than those receiving only gemcitabine. Nab-paclitaxel may enhance gemcitabine's effectiveness by increasing its concentration in tumors. Although these results come from different cancer types, they suggest that this combination could also be effective for sarcomas, which are cancers of the bone and soft tissues. Early studies in labs and with animals have shown promising results for sarcoma, supporting its potential use. Participants in this trial will receive the combination of nab-paclitaxel and gemcitabine to evaluate its effectiveness for sarcoma. ^{1 2 3 4 5}

Who Is on the Research Team?

Javier Oesterheld, M.D.

Principal Investigator

Carolinas Medical Center, Levine Cancer Institute

Are You a Good Fit for This Trial?

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.

Participants must have the ability to understand and the willingness to sign a written informed consent or assent document

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7388541/

Albumin-bound paclitaxel and gemcitabine combination ... In addition, the results of this study demonstrate that the effectiveness of nab-paclitaxel/ gemcitabine is significantly greater than that of conventional ...

2. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2024/PX0354-Nab-Paclitaxel-in-Combo-Gemcitabine_combined.pdf

Bound (Nab)-Paclitaxel (in Combination With Gemcitabine) Huh et al 2 was a multicentre, single-arm, open-label, phase II study conducted in South Korea, evaluating the efficacy and safety of gemcitabine 1,000 mg/m2 ...

3. withpower.com withpower.com/trial/phase-3-osteosarcoma-9-2016-83e67

nab-Paclitaxel + Gemcitabine for Sarcoma Research shows that nab-Paclitaxel and Gemcitabine together have been effective in treating pancreatic cancer and have shown promising results in preclinical ...

4. cancer.gov cancer.gov/types/pancreatic/research/nab-paclitaxel-gemcitabine

Nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic ... Patients who received the drug combination had a median overall survival of 8.5 months, compared with 6.7 months for patients treated with gemcitabine alone.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02023021

Nab-paclitaxel Combined With Gemcitabine as Adjuvant ... Nab-paclitaxel could enhance the intratumoral concentration of gemcitabine; recent studies showed that nab-paclitaxel plus gemcitabine significantly improved ...