Erlotinib + Tyrosine Kinase Inhibitors for Cancer

Overseen By DTC Referral Coordinators

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4/CYP1A2 inhibitors, Gastric pH agents

Disqualifiers: Smoking, Cirrhosis, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

Duration: 28-day cycles, up to 30 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining the drug Erlotinib (a tyrosine kinase inhibitor) with either Lenvatinib or Axitinib can more effectively stop or slow the growth of certain cancers that have returned or spread after initial treatment. Participants will join one of two groups: taking Erlotinib with Lenvatinib or Erlotinib with Axitinib, to identify which combination is most effective. Eligible participants have solid tumors that have progressed despite standard treatments and lack other treatment options. Participants will take their medications at home and attend regular clinic visits to monitor progress. This trial may suit those willing to manage daily medication and participate in regular health assessments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications, specifically strong CYP3A4- and/or CYP1A2-inhibiting or -inducing agents, and agents that increase gastric pH, unless they can be replaced with alternatives. If you are on more than two blood pressure medications, you will also need to adjust your treatment. Please discuss with your doctor to see if your current medications are affected.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have tested erlotinib, axitinib, and lenvatinib for safety in humans. Research shows that axitinib can shrink tumors in some patients, though it may cause side effects like high blood pressure and diarrhea. While generally well-tolerated, it carries some risks.

Studies on lenvatinib also show promising results. Used with other treatments, it has demonstrated an acceptable safety profile, meaning side effects are usually manageable.

Erlotinib combinations aim to stop tumor growth. So far, when used with other treatments, they have not shown unexpected or severe risks. Overall, these drugs have undergone testing and are generally considered safe, but like all treatments, they can have side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine erlotinib with axitinib or lenvatinib, both of which are tyrosine kinase inhibitors that target different pathways in cancer cells. Unlike standard treatments that typically focus on a single pathway, these combinations aim to block multiple growth signals, potentially leading to more effective cancer control. This dual-targeting approach could offer a powerful alternative to existing therapies by reducing the likelihood of cancer cell resistance and delivering more comprehensive treatment outcomes.

What evidence suggests that this trial's treatments could be effective for cancer?

This trial will compare the combination of Erlotinib with Axitinib to Erlotinib with Lenvatinib for treating advanced cancers. Research has shown that combining Erlotinib with Axitinib may be promising. Specifically, one study found that using Axitinib with another drug helped patients live longer without their cancer worsening—15.7 months compared to 11.1 months with a different treatment. Real-world evidence supports these results, showing effectiveness in similar situations.

For the Erlotinib and Lenvatinib combination, studies indicate that Lenvatinib, when used with other treatments, improves survival outcomes. Another study found that Erlotinib reduced the risk of cancer progression by 29%. These findings suggest that using these drugs together might help slow or stop cancer growth. ^{3 4 6 7 8}

Who Is on the Research Team?

Sarah J Shin, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors that have worsened after treatment or for which no standard treatment exists. They must be able to swallow pills, not have severe infections like AIDS, and should have stable vital organ functions. People with certain heart conditions, those on specific drugs that affect the trial medications, smokers, pregnant or breastfeeding women are excluded.

Inclusion Criteria

Patients must have evaluable disease according to RECIST 1.1 criteria.

Patients must have <= 1+ proteinuria on urinalysis, or < 1 g protein on 24-hour urine collection, or a urine protein:creatinine ratio of < 1.

My cancer has worsened despite treatment or there are no standard treatments for it.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs.

Patients who are receiving any investigational agents are excluded.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive erlotinib in combination with either lenvatinib or axitinib in 28-day cycles. Treatment continues as long as it is effective.

28-day cycles, up to 30 months

4 visits during the first cycle, then 1 visit per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Follow-up phone calls

What Are the Treatments Tested in This Trial?

Interventions

• Axitinib
• Erlotinib
• Lenvatinib

Trial Overview The study is testing combinations of oral capsules: Erlotinib with either Lenvatinib or Axitinib in adults to see if these can stop tumor growth or shrink them. Participants will take these medications daily at home and attend clinic visits for monitoring through various tests including imaging scans.

How Is the Trial Designed?

Group I: B Experimental Treatment 2 Interventions

Erlotinib with axitinib combination

Group II: A Experimental Treatment 2 Interventions

Erlotinib with lenvatinib combination

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

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Lenvatinib is an effective oral treatment for various cancers, including thyroid, liver, kidney, and endometrial cancers, and can be used alone or in combination with other therapies, based on extensive clinical trial data.

The dosing strategies for lenvatinib have been carefully established to maximize patient benefits while managing side effects, which are similar to those of other tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies. Motzer, RJ., Taylor, MH., Evans, TRJ., et al.[2023]

In a Phase I study with 15 healthy volunteers, the inhibition of P-glycoprotein (P-gp) by single-dose rifampicin increased the exposure of lenvatinib by approximately 32% for free and 31% for total concentrations, suggesting that P-gp plays a role in lenvatinib pharmacokinetics.

Conversely, multiple-dose rifampicin, which induces both P-gp and CYP3A4, decreased lenvatinib exposure by 18% for total and 9% for free concentrations, but these changes were small and likely not clinically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rifampicin on the pharmacokinetics of lenvatinib in healthy adults. Shumaker, RC., Aluri, J., Fan, J., et al.[2021]

Lenvatinib, a multitargeted Tyrosine Kinase Inhibitor, has shown significant improvement in Progression-Free Survival (PFS) for patients with aggressive Differentiated Thyroid Cancer (DTC) not responsive to radioiodine, with a median PFS of 18.2 months compared to 3.6 months for placebo.

While lenvatinib is effective, it is associated with a high rate of adverse effects (over 40%), including hypertension and fatigue, and about 14% of patients may need to discontinue treatment due to these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib in the Therapy of Aggressive Thyroid Cancer: State of the Art and New Perspectives with Patents Recently Applied. Ferrari, SM., Ruffilli, I., Centanni, M., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4499265/

Pharmacodynamic study of axitinib in patients with ... A significant increase in tumor proliferation was observed during withdrawal of axitinib therapy, and this flare occurred within 2 days of axitinib withdrawal.

2. targetedonc.com targetedonc.com/view/combination-therapies-make-significant-impact-on-advanced-rcc-treatment-across-lines-of-therapy

Combination Therapies Make Significant Impact on ... All the other trials showed a significant median PFS benefit: for axitinib plus pembrolizumab, 15.7 months vs 11.1 months [HR 0.68; 95% CI, 0. ...

3. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer_presents_promising_new_immunotherapy_combination_data_with_inlyta_axitinib_in_advanced_renal_cell_carcinoma_rcc

Pfizer Presents Promising New Immunotherapy ... The study was designed to establish dosing and evaluate the safety and anti-tumor activity of INLYTA when combined with pembrolizumab in first-line treatment ...

4. actionkidneycancer.org actionkidneycancer.org/real-world-experience-with-axitinib-inlyta/

Real world experience with axitinib (Inlyta) The article suggests that the real world efficacy data for axitinib is similar to that seen in clinical trials, with a median overall survival of 16.4 months ...

5. inlyta.pfizerpro.com inlyta.pfizerpro.com/monotherapy/efficacy

INLYTA® (axitinib) Efficacy Measures | 2nd-Line | Safety Info Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3825605/

Axitinib: A Review of its Safety and Efficacy in the ... This paper reviews the mechanism of action of axitinib, its metabolism, and its pharmacokinetic profile. Clinical data of efficacy and safety is also detailed.

7. inlyta.com inlyta.com/axitinib/clinical-trial-results

INLYTA® (axitinib) Clinical Trial Results | Safety Info 70 of 361 patients taking INLYTA saw their tumors shrink compared to 34 of 362 patients taking Nexavar. This includes patients whose tumors shrank 30% or more ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/14796694.2024.2351352

Real-world experience of second-line axitinib in metastatic ... The median OS (95% CI) for all patients who received second-line axitinib was 12.2 (7.7–14.2) months; 28 (25.5%) patients remained censored at ...