Ruxolitinib for Non-Small Cell Lung Cancer Cachexia

Overseen By Jonathan VanPelt

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Tu Dan

Must not be taking: CYP3A4 inhibitors, Fluconazole

Disqualifiers: Stage I-III NSCLC, Actionable mutations, Active malignancy, Uncontrolled illness, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Ruxolitinib, a medication taken by mouth, in patients with advanced lung cancer who suffer from severe weight loss. The drug works by blocking certain signals in the body to help reduce this weight loss and muscle wasting. Ruxolitinib has shown effectiveness in improving symptoms and quality of life in patients.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are taking strong CYP3A4 inhibitors and fluconazole, as these are excluded.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking therapies that are strong CYP3A4 inhibitors and fluconazole. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

What data supports the idea that Ruxolitinib for Non-Small Cell Lung Cancer Cachexia is an effective drug?

The available research does not provide direct evidence that Ruxolitinib is effective for Non-Small Cell Lung Cancer Cachexia. However, studies on other conditions show that Ruxolitinib can lead to weight gain, which might be beneficial for cachexia patients who often suffer from weight loss. For example, in patients with myelofibrosis, Ruxolitinib treatment resulted in significant weight gain over 72 weeks. Additionally, Ruxolitinib has shown potential in combination with other drugs to reduce tumor growth in solid tumors, including lung cancer, suggesting it might have some benefits in cancer treatment. However, more specific research is needed to confirm its effectiveness for Non-Small Cell Lung Cancer Cachexia. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug Ruxolitinib for treating cachexia in non-small cell lung cancer?

Ruxolitinib, a JAK1/2 inhibitor, has been shown to cause weight gain in patients with myelofibrosis, which might suggest potential benefits for cachexia (weight loss and muscle wasting) in non-small cell lung cancer. Additionally, Ruxolitinib has been explored for its anti-cancer effects in solid tumors, including lung cancer, when combined with other treatments. ^{1 2 3 4 5}

What safety data is available for Ruxolitinib?

Ruxolitinib, also known as Jakafi, Jakavi, or Opzelura, has been evaluated for safety in various studies. Common adverse effects include anemia and thrombocytopenia, with some patients experiencing weight gain. In a study with Japanese myelofibrosis patients, 9.8% discontinued due to adverse events, but no deaths occurred. In healthy Japanese volunteers, ruxolitinib was well tolerated, with manageable and reversible decreases in neutrophil counts. Overall, ruxolitinib is considered safe with manageable side effects. ^{1 3 6 7 8}

Is ruxolitinib generally safe for humans?

Ruxolitinib has been studied for safety in both patients with myelofibrosis and healthy volunteers. Common side effects include anemia (low red blood cell count) and thrombocytopenia (low platelet count), but it is generally well tolerated, with most side effects being manageable and reversible. ^{1 3 6 7 8}

Is the drug Ruxolitinib a promising treatment for non-small cell lung cancer cachexia?

The provided research articles do not mention Ruxolitinib or its effects on non-small cell lung cancer cachexia, so we cannot determine if it is a promising treatment based on this information. ^{9 10 11 12 13}

How is the drug Ruxolitinib unique for treating cachexia in non-small cell lung cancer?

Ruxolitinib is unique because it targets specific pathways involved in inflammation and immune response, which may help address cachexia (severe weight and muscle loss) in non-small cell lung cancer, unlike traditional chemotherapy that primarily targets cancer cells. ^{9 10 11 12 13}

Research Team

Tu Dan

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

Adults with advanced Non-Small Cell Lung Cancer and cachexia can join this trial. They must have a life expectancy of at least 6 months, no prior treatment for their lung cancer, and agree to use contraception. Those with certain mutations or other active cancers, previous JAK inhibitor treatments, or serious health issues like heart failure are excluded.

Inclusion Criteria

You have been diagnosed with non-small cell lung cancer, confirmed by a biopsy or tissue sample.

Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for the duration of study participation

You are expected to live for at least 6 more months.

Exclusion Criteria

You are currently taking part in another clinical trial for treating lung or other cancers.

Females who are pregnant, breast-feeding or plan to become pregnant

Any other conditions that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ruxolitinib with dose escalation over 3 months to assess toxicity and impact on cancer cachexia

3 months

Bi-weekly visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life and body weight assessments

1 month

Bi-weekly visits

Long-term Follow-up

Progression-free survival and overall survival assessments at 6 months from start of active phase

6 months

Treatment Details

Interventions

• Ruxolitinib

Trial Overview The trial is testing the safety of Ruxolitinib in treating cachexia in lung cancer patients. It aims to find any toxic effects from different doses and see how it affects signaling pathways related to muscle and fat tissue before and after treatment.

Participant Groups

Group I: Dosing Regimen for Ruxolitinib Experimental Treatment 1 Intervention

Level 0: Ruxolitinib 0 MG po bid for 1 month (Month 1) Level 1: Ruxolitinib 10 MG po bid for 1 month (Month 2) Level 2: Ruxolitinib 15 MG po bid for 1 month (Month 3)

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

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

Tu Dan

Lead Sponsor

Trials

1

Recruited

10+

Puneeth Iyengar

Lead Sponsor

Trials

1

Recruited

10+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

In a pilot study involving two patients with myelofibrosis treated with ruxolitinib, both experienced an increase in waist circumference, indicating weight gain as a side effect of the medication.

The study suggested that the weight gain associated with ruxolitinib may be linked to changes in energy expenditure, as initial increases in energy expenditure were followed by decreases, ultimately remaining below baseline levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Energy expenditure in myelofibrosis patients treated with a JAK1/2 inhibitor. Tremblay, D., Dougherty, M., Mascarenhas, J., et al.[2023]

In a study of 127 patients with myeloproliferative neoplasms treated with ruxolitinib, significant weight gain was observed, with 50% of patients gaining more than 5% body weight over 72 weeks, indicating a notable metabolic effect of the drug.

Ruxolitinib treatment was associated with increased systolic blood pressure and elevated liver enzymes (AST and ALT), suggesting potential long-term metabolic consequences that need to be monitored in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Effects of JAK1/2 Inhibition in Patients with Myeloproliferative Neoplasms. Sapre, M., Tremblay, D., Wilck, E., et al.[2021]

In the COMFORT-I study, ruxolitinib significantly improved metabolic and nutritional status in patients with intermediate-2 or high-risk myelofibrosis, leading to increased weight, cholesterol, and albumin levels compared to placebo.

Ruxolitinib treatment not only reduced spleen size and improved symptoms but also showed sustained benefits in metabolic parameters over time, indicating its potential as a comprehensive treatment for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I. Mesa, RA., Verstovsek, S., Gupta, V., et al.[2021]

Ruxolitinib, a drug approved for myelofibrosis, shows potential as an anti-cancer agent when combined with ERBB1/2/4 inhibitors, effectively killing various solid tumor cells, including breast and lung cancers.

The combination therapy triggers significant cellular mechanisms, including mitophagy and the activation of apoptosis pathways, leading to reduced tumor growth in preclinical models, suggesting it warrants further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationally Repurposing Ruxolitinib (Jakafi (®)) as a Solid Tumor Therapeutic. Tavallai, M., Booth, L., Roberts, JL., et al.[2023]

Ruxolitinib, a JAK1/2 inhibitor, was evaluated in a Phase Ib study with 42 patients, primarily with pancreatic cancer, showing it was generally safe and well tolerated when combined with gemcitabine, although the study was terminated early due to interim results from another study.

The overall response rate for the combination therapy was 38.5% in the pooled cohorts, but the study was halted before determining maximum tolerated doses, indicating that while there was some efficacy, the combination will not be pursued further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors. Bauer, TM., Patel, MR., Forero-Torres, A., et al.[2022]

Ruxolitinib, a drug for treating intermediate or high-risk myelofibrosis, was studied in a population of 272 subjects, revealing that its pharmacokinetics can be accurately described by a two-compartment model, indicating effective absorption and elimination.

The study found that while gender and body weight influence the drug's clearance and distribution, these effects are not clinically significant, meaning no dose adjustments are necessary based on these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of orally-administered ruxolitinib (INCB018424 Phosphate) in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET MF). Chen, X., Williams, WV., Sandor, V., et al.[2021]

Ruxolitinib is shown to be safe and effective for treating myelofibrosis in Japanese patients, with 86.3% of the 51 participants completing the 24-week study and no deaths reported.

At 24 weeks, 30% of patients had significant reductions in spleen size, and there were notable improvements in symptoms and quality of life, even among those with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis. Komatsu, N., Kirito, K., Shimoda, K., et al.[2021]

Ruxolitinib, an oral Janus kinase inhibitor, was found to be rapidly absorbed and well tolerated in a study involving 40 Japanese subjects, with no significant safety concerns reported.

The study showed that ruxolitinib's pharmacokinetics were similar in Japanese participants compared to non-Japanese populations, indicating consistent efficacy and safety across different ethnic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized dose-escalation study to assess the safety, tolerability, and pharmacokinetics of ruxolitinib (INC424) in healthy Japanese volunteers. Ogama, Y., Mineyama, T., Yamamoto, A., et al.[2022]

In a study of 65 patients with advanced non-small cell lung cancer, those receiving molecular targeted therapies (EGFR and ALK TKIs) experienced significantly less skeletal muscle loss compared to those undergoing cytotoxic chemotherapy.

The analysis showed that the loss of muscle area was notably higher in the chemotherapy group, indicating that TKIs may be a safer option in terms of preserving muscle mass during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in skeletal muscle loss caused by cytotoxic chemotherapy and molecular targeted therapy in patients with advanced non-small cell lung cancer. Kakinuma, K., Tsuruoka, H., Morikawa, K., et al.[2018]

In a study of 47 patients with T790M-positive advanced non-small cell lung cancer (NSCLC), body size variables like body surface area (BSA) and body mass index (BMI) did not significantly affect the efficacy of osimertinib, with similar response rates and progression-free survival across different body size groups.

The study found that osimertinib's effectiveness remained consistent regardless of body size, and factors such as better performance status, younger age, and specific genetic mutations (EGFR exon 19 deletion) were identified as more important predictors of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of osimertinib efficacy according to body surface area and body mass index in patients with non-small cell lung cancer harboring an EGFR mutation: A prospective observational study. Ono, T., Igawa, S., Ozawa, T., et al.[2022]

Erlotinib showed slightly better outcomes than gefitinib in treating non-small cell lung cancer (NSCLC), although the differences were not statistically significant, indicating that both drugs are viable options.

Molecular markers such as high levels of phosphorylated EGFR (pEGFR), pAKT, and pSTAT3 were associated with longer time to progression in patients, suggesting that tumors with these activated pathways may respond better to treatment with tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to gefitinib and erlotinib in Non-small cell lung cancer: a restrospective study. Emery, IF., Battelli, C., Auclair, PL., et al.[2021]

In three cases of advanced bronchioloalveolar carcinoma, treatment with 250 mg of Gefitinib (Iressa) once daily resulted in significant antitumor effects.

Gefitinib showed remarkable clinical responses in patients with poor performance status who had previously undergone extensive chemotherapy, suggesting its potential as an effective treatment option in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gefitinib for advanced bronchioloalveolar carcinoma]. Zhang, XT., Wang, SL., Li, LY.[2018]

Gefitinib has shown antitumor activity in lung cancer patients, with phase I trials indicating it is well tolerated at doses effective for treatment, leading to objective response rates of 10-20% in phase II trials with minimal toxicity.

While combining gefitinib with chemotherapy in phase III trials did not improve survival rates for patients with advanced non-small cell lung cancer, it did not significantly increase overall toxicity, suggesting potential for further studies with different treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gefitinib (Iressa) trials in non-small cell lung cancer. Johnson, DH.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Energy expenditure in myelofibrosis patients treated with a JAK1/2 inhibitor. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Metabolic Effects of JAK1/2 Inhibition in Patients with Myeloproliferative Neoplasms. [2021]

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

Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Rationally Repurposing Ruxolitinib (Jakafi (®)) as a Solid Tumor Therapeutic. [2023]

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

A Phase Ib study of ruxolitinib + gemcitabine ± nab-paclitaxel in patients with advanced solid tumors. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of orally-administered ruxolitinib (INCB018424 Phosphate) in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET MF). [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

A randomized dose-escalation study to assess the safety, tolerability, and pharmacokinetics of ruxolitinib (INC424) in healthy Japanese volunteers. [2022]

9. Singapore pubmed.ncbi.nlm.nih.gov

Differences in skeletal muscle loss caused by cytotoxic chemotherapy and molecular targeted therapy in patients with advanced non-small cell lung cancer. [2018]

10. Singapore pubmed.ncbi.nlm.nih.gov

Evaluation of osimertinib efficacy according to body surface area and body mass index in patients with non-small cell lung cancer harboring an EGFR mutation: A prospective observational study. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Response to gefitinib and erlotinib in Non-small cell lung cancer: a restrospective study. [2021]

12. China pubmed.ncbi.nlm.nih.gov

[Gefitinib for advanced bronchioloalveolar carcinoma]. [2018]

13. Ireland pubmed.ncbi.nlm.nih.gov

Gefitinib (Iressa) trials in non-small cell lung cancer. [2019]