Iadademstat + Paclitaxel for Lung Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Namrata Vijavergia

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Fox Chase Cancer Center

Must not be taking: LSD1 inhibitors

Disqualifiers: More than 3 therapies, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a non-randomized single-arm, two cohorts, phase II study of iadademstat in combination with weekly paclitaxel in patients with relapse/refractory SCLC or extrapulmonary G3 Neuroendocrine Carcinomas. A total of 42 patients with SCLC (21 patients) and G3 NEC (21 patients) will be enrolled (including those enrolled in the safety lead-in portion).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take medications with LSD1 inhibitory activity (like tranylcypromine or phenelzine) within 3 weeks of starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Iadademstat and Paclitaxel for lung cancer?

Paclitaxel has shown effectiveness in treating lung cancer, with studies reporting response rates of up to 41% in non-small cell lung cancer. It is often used in combination with other drugs, like platinum compounds, to enhance its effectiveness. ^{1 2 3 4 5}

Is the combination of Iadademstat and Paclitaxel safe for humans?

Paclitaxel, also known as Taxol, has been used in various cancer treatments and is generally considered safe with manageable side effects like neutropenia (low white blood cell count) and neuropathy (nerve damage). Abraxane, a form of Paclitaxel, has been shown to be safe in treating lung cancer, with side effects reduced by premedication. ^{1 2 5 6 7}

How is the drug combination of Iadademstat and Paclitaxel unique for treating lung cancer?

The combination of Iadademstat and Paclitaxel for lung cancer is unique because it involves Iadademstat, a novel drug that may work differently from traditional chemotherapy agents, potentially offering a new mechanism of action. Paclitaxel is already known for its effectiveness in lung cancer, and combining it with Iadademstat could enhance its effects or provide benefits not seen with existing treatments. ^{1 2 5 8 9}

Research Team

Namrata Vijavergia

Principal Investigator

Fox Chase Cancer Center

Eligibility Criteria

This trial is for adults over 18 with certain types of advanced cancers, including relapsed/refractory SCLC and high-grade extrapulmonary neuroendocrine carcinomas. Participants must have had platinum-based chemo but no taxane therapy unless it was over six months prior as neoadjuvant/adjuvant treatment. They should be able to swallow pills, not have severe infections or other health conditions that could interfere with the study, and agree to use effective contraception.

Inclusion Criteria

I can swallow pills and keep them down.

I am a male willing to follow strict rules for preventing pregnancy during and 6 months after the study.

I've had platinum-based chemo and up to 3 treatments for advanced cancer, but no taxane unless it was over 6 months ago.

Exclusion Criteria

I am not allergic to iadademstat, paclitaxel, or their ingredients.

I haven't had taxane-based treatments for my condition in the last 6 months, except as part of early cancer treatment.

I have not had surgery or significant injury within the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

A safety lead-in phase with 12 patients to assess initial safety and tolerability

6 weeks

Weekly visits for treatment and monitoring

Treatment

Participants receive iadademstat and paclitaxel in a 21-day cycle with weekly administration

2 years

Weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Iadademstat (Histone Methyltransferase Inhibitor)
• Paclitaxel (Mitotic Inhibitor)

Trial Overview The trial tests iadademstat combined with weekly paclitaxel in patients who've seen their cancer return or resist previous treatments. It's a phase II study involving two groups: one with small cell lung cancer (SCLC) and another with grade 3 neuroendocrine carcinomas (G3 NEC), each having 21 patients.

Participant Groups

Group I: Iadademstat plus Paclitaxel Experimental Treatment 2 Interventions

Iadademstat oralon a 5 day ON and 2-day OFF schedule every week plus Paclitaxel administered intravenously weekly on day 1, 8 and 15 on day 1 of a 21 day treatment cycle.

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Dr. James Helstrom

Fox Chase Cancer Center

Chief Medical Officer since 2014

MD from University of Colorado School of Medicine, MBA from Washington University in St. Louis

Dr. Robert Uzzo

Fox Chase Cancer Center

Chief Executive Officer since 2022

MD from Cleveland Clinic, MBA

Oryzon Genomics S.A.

Industry Sponsor

Trials

5

Recruited

350+

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 study of 599 chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC), the combination of paclitaxel and cisplatin showed superior survival rates compared to the standard etoposide and cisplatin regimen, with a median survival of 9.9 months versus 7.6 months, respectively.

While both regimens had similar toxicity profiles, the low-dose paclitaxel regimen was associated with increased granulocytopenia, and the high-dose regimen showed potential for increased neurotoxicity and cardiac events, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. Bonomi, P., Kim, K., Fairclough, D., et al.[2022]

Single-agent paclitaxel shows a notable 35% to 40% one-year survival rate in patients with advanced metastatic non-small cell lung cancer (NSCLC), indicating its efficacy as a cytotoxic agent.

Combination therapies involving paclitaxel, particularly with adjusted administration schedules, can improve response rates and reduce severe side effects like neutropenia, making it a viable option for patients who cannot tolerate platinum-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent paclitaxel and paclitaxel/non-platinum combination therapy in advanced non-small cell lung cancer. Socinski, MA., Langer, CJ.[2022]

In a study of 33 patients with progressive or recurrent non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, Abraxane showed a partial response rate of 33.3%, with better outcomes in patients with squamous cell carcinoma (41.7% response) compared to those with adenocarcinoma (21.1%).

The treatment demonstrated a disease control rate of 75.8% and a median progression-free survival of five months, with manageable side effects, indicating that Abraxane is a potentially effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. Yuan, DM., Lv, YL., Yao, YW., et al.[2019]

Paclitaxel, a novel antineoplastic drug, has shown significant effectiveness in treating advanced cancers such as ovarian, breast, non-small cell lung cancer, and head and neck cancer, with a potential to become a first-line treatment when combined with platinum for advanced ovarian cancer.

While initial hypersensitivity reactions posed challenges, current premedication strategies have reduced these side effects to less than 3%, although neutropenia remains a major dose-limiting adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. Hájek, R., Vorlicek, J., Slavik, M.[2015]

References

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

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

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

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

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

Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. [2022]

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

Single-agent paclitaxel and paclitaxel/non-platinum combination therapy in advanced non-small cell lung cancer. [2022]

6. Singapore pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. [2019]

7. Slovakia pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]

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

Combination paclitaxel and platinum in the treatment of lung cancer: US experience. [2015]

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

Defining the role of paclitaxel in lung cancer: summary of recent studies and implications for future directions. [2015]