Radiotherapy + Abraxane for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Edgar Ben-Josef, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Disqualifiers: Distant metastases, Prior abdominal radiation, Others

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

Compensation: Varies

Number of Visits: 2

42 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that chemotherapy before and/or after the trial may be given as per standard care, which suggests that some medications might be continued. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Radiotherapy + Abraxane for Pancreatic Cancer?

Nab-paclitaxel (Abraxane) has shown effectiveness in treating metastatic pancreatic cancer when combined with another drug, gemcitabine, and is FDA-approved for this use. It is also considered a promising radiosensitizer, meaning it may enhance the effects of radiation therapy, although it has not been clinically tested with definitive radiotherapy for locally advanced pancreatic cancer. ^{1 2 3 4 5}

Is the combination of radiotherapy and nab-paclitaxel (Abraxane) generally safe for humans?

Nab-paclitaxel (Abraxane) is FDA-approved for several cancers and has been tested with radiotherapy in pancreatic cancer. It has shown less severe side effects like neutropenia (low white blood cell count), neuropathy (nerve damage), and muscle/joint pain compared to other treatments, but may cause more thrombocytopenia (low platelet count) and anemia (low red blood cell count). ^{1 2 4 6 7}

How is the treatment of Radiotherapy + Abraxane for pancreatic cancer different from other treatments?

This treatment is unique because it combines nab-paclitaxel (Abraxane), which is known to enhance the effects of radiation therapy, with radiotherapy to potentially improve outcomes for patients with locally advanced pancreatic cancer, a combination not previously tested in this setting. ^{1 2 3 5 6}

What is the purpose of this trial?

The investigators hypothesize that intensification of local therapy will lead to improvements in local control and survival in patients with unresectable and borderline resectable pancreatic cancer. We propose to do this by combining nab-paclitaxel concurrently with dose-escalated radiation therapy. In the first part of this phase I study (sub-trial 1), the nab-paclitaxel dose will be escalated while the radiation dose is held constant at a standardly accepted level. The use of this novel chemoradiotherapy regimen will take advantage of nab-paclitaxel's specific anti-tumor and anti-stromal properties, which may enhance the efficacy of radiation therapy, and thereby improve local control. After the MTD of nab-paclitaxel had been determined, a second arm in sub-trial 1 will evaluate the addition of paricalcitol to nab-paclitaxel concurrently with dose-escalated radiation therapy. In addition, after the MTD of the nab-paclitaxel is reached in sub-trial 1 arm A, in the second part of this study (sub-trial 2), we will administer nab-paclitaxel at the determined MTD concurrently with escalated doses of radiation. We will utilize IMRT or protons to safely deliver high doses of radiation while maximally sparing surrounding normal tissue. Patients will also preferentially have 2-3 fiducial markers placed in or around the tumor for daily localization. Chemotherapy before and/or after chemoradiotherapy may be given as per standard of care. Correlative tissue and serum biomarkers are an important, but optional, part of this study.

Research Team

Edgar Ben-Josef, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

This trial is for adults over 18 with a specific type of pancreatic cancer that can't be removed by surgery or is borderline removable. They should be relatively healthy, able to consent, and willing to use birth control if they can have children. People with spread-out cancer, previous abdominal radiation, other recent cancers, or who are pregnant/nursing cannot join.

Inclusion Criteria

My cancer is a type of pancreatic cancer called adenocarcinoma.

My condition is considered inoperable or nearly inoperable by a team of doctors.

Patients must be able to provide written informed consent

Exclusion Criteria

Pregnant women, women planning to become pregnant, and nursing women

Treatment with an investigational anti-cancer agent within 4 weeks prior to enrollment

My cancer has spread to distant parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy and Radiation

Nab-paclitaxel dose escalation with concurrent dose-escalated radiation therapy to determine maximum tolerated dose (MTD)

6-8 weeks

Weekly visits for dose escalation monitoring

Chemotherapy and Radiation with Paricalcitol

Evaluation of the addition of paricalcitol to nab-paclitaxel with dose-escalated radiation therapy

6-8 weeks

Weekly visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• nab-paclitaxel
• Radiotherapy

Trial Overview The study tests increasing doses of nab-paclitaxel (Abraxane) combined with constant-dose radiation therapy in one part and then combines the best dose found with higher-dose radiation in another part. It aims to see if this combo improves survival and tumor control.

Participant Groups

Group I: Subtrial 2- Abraxane 125mg; Borderline get 55cGY, unresectable get 57.5cGY until next escalation Experimental Treatment 2 Interventions

Group II: Subtrial 1-Arm B (Dose Level 2 of Abraxane: 3+4 enrollment) Experimental Treatment 2 Interventions

Determine the maximum dose of Abraxane that is allowable and safe for patients receiving both Abraxane and radiation therapy.

Group III: Subtrial 1-Arm A (Dose Level 1 of Abraxane) Experimental Treatment 2 Interventions

Determine if it is safe or not (via occurrence of dose limiting toxicities) for patients to receive both Abraxane and radiation therapy.

nab-paclitaxel is already approved in United States, European Union for the following indications:

Approved in United States as Abraxane for:

• Metastatic pancreatic adenocarcinoma

Approved in European Union as Abraxane for:

• Metastatic pancreatic adenocarcinoma

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Findings from Research

In a phase 1 study involving 9 patients with locally advanced pancreatic cancer, the combination of weekly nab-paclitaxel and daily radiotherapy was found to be safe and well-tolerated, with minimal severe side effects.

After treatment, 4 patients were able to undergo surgical resection with negative margins, indicating a significant treatment effect and limited tumor viability, suggesting potential for improved outcomes in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. Shabason, JE., Chen, J., Apisarnthanarax, S., et al.[2022]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., 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]

Nab-paclitaxel (Abraxane) is an effective treatment for metastatic breast cancer, showing a superior therapeutic index compared to conventional paclitaxel in a Phase III study with a standard dose of 260 mg/m² every three weeks.

In patients with poor prognostic factors, nab-paclitaxel demonstrated rapid and significant tumor responses, indicating it may be particularly beneficial for those with more severe disease, and lower doses (100 and 150 mg/m² weekly) also showed promising efficacy, suggesting potential for dose tailoring in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the role of nab-paclitaxel (Abraxane) in women with aggressive metastatic breast cancer. Ciruelos, E., Jackisch, C.[2015]

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 I trial involving 14 patients with unresectable locally advanced pancreatic cancer, the maximum tolerated dose (MTD) of nab-paclitaxel combined with external beam radiotherapy (EBRT) was determined to be 75 mg/m², as doses above this led to significant toxicities.

The treatment was generally well-tolerated, with common side effects including nausea and fatigue, and resulted in a median progression-free survival of 4.7 months and overall survival of 10.8 months, indicating potential efficacy in this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of nab-Paclitaxel Administered Concurrently With Radiotherapy in Patients With Locally Advanced Inoperable Pancreatic Adenocarcinoma. Roy, AC., Abbas, MN., Price, TJ., et al.[2023]

Nab-paclitaxel (Abraxane(®)) combined with carboplatin has been approved for treating advanced non-small-cell lung cancer (NSCLC) and showed a significantly improved overall response rate compared to traditional solvent-based paclitaxel in a Phase III trial.

Patients receiving nab-paclitaxel experienced fewer side effects such as neutropenia and neuropathy, making it a safer option, although it was associated with more thrombocytopenia and anemia compared to solvent-based paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-paclitaxel for the management of patients with advanced non-small-cell lung cancer. Hirsh, V.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. [2022]

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

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). [2022]

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

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

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

Evaluating the role of nab-paclitaxel (Abraxane) in women with aggressive metastatic breast cancer. [2015]

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

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

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

Phase I Trial of nab-Paclitaxel Administered Concurrently With Radiotherapy in Patients With Locally Advanced Inoperable Pancreatic Adenocarcinoma. [2023]

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

nab-paclitaxel for the management of patients with advanced non-small-cell lung cancer. [2022]