SMS001 (Paclitaxel) for Lung Cancer

Overseen By Jennifer Lister / Clinical Research Coordinator / UHN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ToLymph Inc.

Disqualifiers: Advanced NSCLC, Previous malignancy, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

42 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the use of SMS001 in patients with lung cancer. SMS001 is a new form of drug Paclitaxel. Doctors want to decide an appropriate safe dose for SMS001 administration, and to see how well it works in treating lung cancer patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial excludes patients with certain health conditions and those who have had prior chemotherapy or radiation, it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug SMS001 (Paclitaxel) for lung cancer?

Research shows that Paclitaxel, a component of SMS001, has been effective in treating various types of lung cancer. In studies, it has shown response rates of 21% to 34% in non-small cell and small cell lung cancer, and it has been used successfully in combination with other treatments. ^{1 2 3 4 5}

Is paclitaxel (Taxol) safe for humans?

Paclitaxel (Taxol) has been studied in many patients and is generally safe, but it can cause side effects like low white blood cell counts, allergic reactions, and mild nerve damage. Serious heart issues are rare, and allergic reactions can be managed with premedication. ^{1 6 7 8 9}

How is the drug SMS001 (Paclitaxel) unique in treating lung cancer?

SMS001 (Paclitaxel) is unique because it can be used in combination with platinum-based drugs or as an albumin-bound form (Abraxane) to reduce severe side effects like neutropenia (low white blood cell count). It also has a radiosensitizing effect, meaning it can make cancer cells more sensitive to radiation therapy, potentially improving treatment outcomes. ^{2 10 11 12 13}

Research Team

Kazuhiro Yasufuku, MD, PhD

Principal Investigator

University Health Network (UHN)

Eligibility Criteria

This trial is for individuals with non-small cell lung cancer. Specific eligibility criteria are not provided, so it's important to contact the study organizers for detailed requirements.

Inclusion Criteria

My lung cancer diagnosis was confirmed through tissue examination.

I am over 18 and fit for lung cancer surgery.

QT interval corrected for heart rate using Frederica's formula (QTcF): males < 450msec and females < 470msec

Exclusion Criteria

I have not had cancer in the last 5 years, except for non-melanoma skin cancer.

My lung cancer is advanced or has spread to distant areas.

I need a major lung surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time administration of SMS001 during their scheduled lung cancer surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of treatment-emergent adverse events

52 weeks

Regular visits as per study protocol

Long-term follow-up

Evaluation of tumor recurrence and disease-free survival at 12-month follow-up

1 year

Treatment Details

Interventions

• SMS001

Trial Overview The trial is testing SMS001, a new version of the drug Paclitaxel, to determine a safe dosage and its effectiveness in treating non-small cell lung cancer.

Participant Groups

Group I: Dose Escalation and Confirmation Experimental Treatment 1 Intervention

All participants will receive a one-time administration of SMS001 undergoing their scheduled lung cancer surgery. Participants are given SMS001 and are watched very closely for side effects. If the side effects are manageable, then more participants are asked to join the study and are given a higher dose of SMS001, until a pre-defined suitable dose is reached.

SMS001 is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Lung cancer
• Kaposi's sarcoma
• Cervical cancer
• Pancreatic cancer

Approved in United States as Taxol for:

• Breast cancer
• Pancreatic cancer
• Ovarian cancer
• Kaposi's sarcoma
• Non-small-cell lung cancer

Approved in United States as Abraxane for:

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

Approved in Canada as Taxol for:

• Ovarian cancer
• Breast cancer
• Lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

ToLymph Inc.

Lead Sponsor

Trials

1

Recruited

40+

University Health Network (UHN)

Collaborator

Trials

1

Recruited

40+

Ozmosis Research Inc.

Industry Sponsor

Trials

25

Recruited

5,200+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Findings from Research

Paclitaxel (TAXOL) has shown promising efficacy in treating lung cancer, with objective response rates of 21% and 24% in patients with non-small cell lung cancer, and a higher response rate of 34% in patients with extensive-stage small cell lung cancer.

Further research is necessary to explore the effectiveness of paclitaxel as a standalone treatment for small cell lung cancer and its potential as a radiosensitizer or in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of paclitaxel (Taxol) in advanced lung cancer. Ettinger, DS.[2015]

In a phase II study involving 34 patients with stage IIIb-IV non-small cell lung cancer, the combination of paclitaxel and vinorelbine resulted in a promising overall response rate of 67.7%, with 16.1% achieving a complete response.

Despite significant side effects, including leukopenia in 48.4% and anemia in 45.4% of patients, the treatment led to a median survival time of 10 months and a 1-year survival rate of 45.1%, indicating its potential as a first-line therapy for non-operable NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of non-platinum based chemotherapy with paclitaxel and vinorelbine in non-small cell lung cancer. Ginopoulos, P., Kontomanolis, E., Kardamakis, D., et al.[2019]

The combination of paclitaxel and vinorelbine was effective as a first-line treatment for untreated patients with metastatic lung adenocarcinoma, with a response rate of 50% and a median survival of 10 months based on a study of 54 patients.

While myelotoxicity was a common side effect affecting 87% of patients, severe neutropenia (grade 4) occurred in only 14.8%, indicating that the treatment regimen was manageable and did not require dose reductions for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and vinorelbine combination in advanced inoperable adenocarcinoma of the lung: a phase II study. Stathopoulos, GP., Veslemes, M., Georgatou, N., et al.[2018]

In a preliminary phase II study involving 23 patients with unresectable stage IIIA or IIIB non-small cell lung cancer, 8 out of 15 patients who completed treatment achieved complete or near-complete responses, indicating promising efficacy of the combined therapy with paclitaxel, cisplatin, etoposide, and radiotherapy.

The treatment regimen was generally well tolerated, although 8 patients experienced grade 3 or 4 esophagitis, primarily during the last two weeks of radiation, highlighting the need for monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel by 1-hour infusion in combination chemotherapy of stage III non-small cell lung cancer. Greco, FA., Stroup, SL., Hainsworth, JD.[2015]

The addition of paclitaxel to cisplatin/etoposide chemotherapy and concurrent thoracic radiotherapy in patients with limited-stage small-cell lung cancer resulted in a high overall response rate of 92%, with 81% achieving complete remission, indicating strong efficacy of this treatment regimen.

While the treatment was effective, it was associated with significant hematologic toxicity, including severe leukopenia in 74% of patients and one treatment-related death, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung cancer. Bremnes, RM., Sundstrøm, S., Vilsvik, J., et al.[2017]

In a multi-institutional early phase II study involving 15 patients with non-small cell lung cancer, BMS-181339 (paclitaxel) showed a partial response rate of 20%, indicating potential efficacy as a treatment.

The treatment was associated with significant side effects, including severe leukopenia in 73.3% of patients and neutropenia in 93.3%, but no serious hypersensitivity reactions were reported, suggesting that while the drug has potential, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Early phase II study of BMS-181339 (paclitaxel) in patients with non-small cell lung cancer. BMS-181339 Non-Small Cell Lung Cancer Study Group]. Yoneda, S., Nishiwaki, Y., Niitani, H., et al.[2015]

Taxol, when administered intravenously, has a well-established safety profile based on data from 655 patients, with myelosuppression, particularly neutropenia, identified as the main dose-limiting toxicity, which was less severe with a 3-hour infusion schedule.

Severe hypersensitivity reactions were effectively managed with a premedication regimen, and while mild to moderate peripheral neuropathy was observed, it rarely led to treatment discontinuation, indicating a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Taxol safety. Onetto, N., Canetta, R., Winograd, B., et al.[2015]

Taxol (paclitaxel) is an effective chemotherapy drug for various cancers, including ovarian and breast cancer, but it can cause severe hypersensitivity reactions and other significant side effects like cardiotoxicity and myelosuppression.

Due to the environmental concerns of sourcing Taxol from the western yew tree, researchers are investigating semisynthetic alternatives like taxotere to provide similar therapeutic benefits with potentially reduced ecological impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxol: a promising new drug of the '90s. Rogers, BB.[2015]

Taxol has shown significant effectiveness in treating advanced ovarian carcinoma, particularly in patients who are resistant to cisplatin, despite its slow clinical development due to hypersensitivity reactions and supply issues.

While premedications have reduced hypersensitivity reactions, there are concerns about potential cardiotoxicity, with 29% of patients experiencing asymptomatic bradycardia and 5% showing more serious cardiac disturbances, necessitating caution in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac disturbances during the administration of taxol. Rowinsky, EK., McGuire, WP., Guarnieri, T., et al.[2017]

In a study of 29 patients with advanced lung cancer, a combination of domestic paclitaxel and other chemotherapy agents resulted in a partial response rate of 31%, indicating some effectiveness in treating the disease.

The treatment was associated with significant adverse effects, particularly hematological toxicity and nausea/vomiting, affecting 90.3% of patients, but these effects were considered tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Domestic paclitaxel-based regimens in the treatment of 31 patients with advanced lung cancer]. Qu, F., Wang, B., Hu, X.[2011]

Paclitaxel has demonstrated strong antitumor activity in various cancers, including ovarian, breast, and lung carcinoma, especially when combined with platinum compounds like cisplatin and carboplatin.

Recent large randomized trials in Europe have explored the effectiveness of paclitaxel in combination with platinum for treating non-small cell lung cancer, showing promising results and leading to ongoing studies on its use in preoperative settings and with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer. Novello, S., Le Chevalier, T.[2019]

In a phase I study involving 22 patients with locally advanced, inoperable non-small cell lung cancer, the combination of paclitaxel and radiation therapy was well tolerated, with no severe adverse events linked to the treatment.

Among the 18 evaluable patients, there was one complete remission and ten partial remissions, indicating that this combined treatment approach may be an effective option for managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and simultaneous radiation in locally advanced stage IIIA/B non-small cell lung cancer: a clinical phase I study. Vogt, HG., Kolotas, C., Martin, T., et al.[2015]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

References

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

Overview of paclitaxel (Taxol) in advanced lung cancer. [2015]

2. Ireland pubmed.ncbi.nlm.nih.gov

A phase II study of non-platinum based chemotherapy with paclitaxel and vinorelbine in non-small cell lung cancer. [2019]

3. Greece pubmed.ncbi.nlm.nih.gov

Paclitaxel and vinorelbine combination in advanced inoperable adenocarcinoma of the lung: a phase II study. [2018]

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

Paclitaxel by 1-hour infusion in combination chemotherapy of stage III non-small cell lung cancer. [2015]

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

Multicenter phase II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung cancer. [2017]

6. Japan pubmed.ncbi.nlm.nih.gov

[Early phase II study of BMS-181339 (paclitaxel) in patients with non-small cell lung cancer. BMS-181339 Non-Small Cell Lung Cancer Study Group]. [2015]

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

Overview of Taxol safety. [2015]

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

Taxol: a promising new drug of the '90s. [2015]

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

Cardiac disturbances during the administration of taxol. [2017]

10. China pubmed.ncbi.nlm.nih.gov

[Domestic paclitaxel-based regimens in the treatment of 31 patients with advanced lung cancer]. [2011]

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

European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer. [2019]

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

Paclitaxel and simultaneous radiation in locally advanced stage IIIA/B non-small cell lung cancer: a clinical phase I study. [2015]

13. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]