Erlotinib + Cabozantinib for Non-Small Cell Lung Cancer

Not currently recruiting at 426 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well the drugs erlotinib and cabozantinib (also known as Cabometyx or Cometriq) work alone or together in treating stage IV non-small cell lung cancer. Both drugs block certain enzymes to stop cancer cell growth. Eligible participants include those with stage IV non-small cell lung cancer and measurable disease who have already undergone one or two chemotherapy treatments. The trial will test the drugs separately and in combination to determine the most effective approach. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must not be on strong CYP3A4 inducers or therapeutic doses of certain anticoagulants. If you are taking any of these, you may need to stop or adjust them before joining the trial.

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

Research has shown that erlotinib hydrochloride is usually well-tolerated by people with non-small cell lung cancer. Common side effects include mild to moderate skin rash and diarrhea, which past studies indicate can usually be managed.

For cabozantinib-s-malate, most safety information comes from patients with advanced kidney cancer. These patients experienced side effects like tiredness and changes in liver function, but adjustments to their medication usually managed these issues.

Limited safety information exists for using both drugs together. However, since both drugs have been studied separately, they might have similar side effects when combined. This trial phase suggests the treatments are considered safe enough for further testing in people.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Erlotinib and Cabozantinib for treating non-small cell lung cancer because these drugs target cancer in unique ways. Erlotinib is a tyrosine kinase inhibitor that blocks signals the cancer cells need to grow, while Cabozantinib inhibits multiple pathways, including VEGFR and MET, which are involved in tumor angiogenesis and growth. This dual-action approach could potentially overcome resistance seen with standard treatments that typically focus on a single target. By combining these mechanisms, this treatment may offer a more comprehensive attack on cancer cells, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Studies have shown that erlotinib can help patients with non-small cell lung cancer live longer and feel better by blocking certain proteins on cancer cells, which helps stop their growth. Cabozantinib has also shown promise in treating advanced non-small cell lung cancer by slowing the disease. In this trial, some participants will receive erlotinib alone, while others will receive cabozantinib alone. Another treatment arm will provide both erlotinib and cabozantinib together, which might be more effective because both target enzymes that cancer cells need to grow. Early research suggests this combination can provide significant benefits. The available evidence supports a hopeful outlook for these treatments in fighting this type of lung cancer.678910

Who Is on the Research Team?

JW

Joel W Neal

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with Stage IV non-small cell lung cancer who have a specific mutation in the EGFR gene, have received 1-2 prior chemotherapy treatments, and can swallow tablets. They should not have had certain previous cancer therapies or major health issues that could affect their participation.

Inclusion Criteria

Your heart's electrical activity, measured by the QT interval, should be less than 500 milliseconds.
Discontinued treatment with any other type of investigational agent >= 4 weeks prior to registration
Your disease can be measured using specific guidelines for evaluating tumor response.
See 13 more

Exclusion Criteria

I am HIV positive and on antiretroviral therapy.
I have been diagnosed with chronic active hepatitis B.
I am currently taking certain medications.
See 16 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive erlotinib, cabozantinib, or both, orally daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle, ongoing until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for 2 years, then every 6 months for up to 5 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Cabozantinib S-malate
  • Erlotinib Hydrochloride
Trial Overview The study is testing how well erlotinib hydrochloride and cabozantinib-s-malate work alone or together as second or third line therapy for patients. These drugs block enzymes needed by tumor cells to grow, but it's unclear if combining them offers better results.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Arm Z (erlotinib+cabozantinib; step II)Experimental Treatment3 Interventions
Group II: Arm C (erlotinib+cabozantinib)Experimental Treatment3 Interventions
Group III: Arm B (cabozantinib)Experimental Treatment2 Interventions
Group IV: Arm A (erlotinib)Experimental Treatment2 Interventions

Cabozantinib S-malate is already approved in United States, European Union for the following indications:

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Approved in United States as Cabometyx for:
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Approved in United States as Cometriq for:
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Approved in European Union as Cabometyx for:

Find a Clinic Near You

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

Cabozantinib demonstrated clinical activity in patients with non-small-cell lung carcinoma (NSCLC), showing a 10% objective response rate and a 38% overall disease-control rate after 12 weeks of treatment, particularly in patients with KRAS mutations.
The treatment was associated with manageable safety concerns, with common grade 3/4 adverse events including fatigue and palmar-plantar erythrodysesthesia, although there was one serious treatment-related adverse event (hemorrhage) reported.
Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non-small-cell Lung Carcinoma.Hellerstedt, BA., Vogelzang, NJ., Kluger, HM., et al.[2019]
In a phase Ib/II study involving 64 patients with progressive non-small cell lung cancer (NSCLC) who had previously received erlotinib, cabozantinib alone showed a modest objective response rate (ORR) of 8.2%, indicating some efficacy as a treatment option.
However, in the phase II portion, the combination of cabozantinib and erlotinib did not yield any responses in patients with acquired resistance to erlotinib, suggesting that cabozantinib did not effectively re-sensitize these patients to erlotinib.
A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer.Wakelee, HA., Gettinger, S., Engelman, J., et al.[2023]

Citations

Effective Treatment with Cabozantinib in an Advanced Non ...We report the first case of cabozantinib effectiveness in treating a CD74-ROS1-positive advanced NSCLC patient. Crizotinib remained as an effective therapeutic ...
ASCO 2022: New Cabometyx® data show encouraging ...These data show that the therapeutic potential of Cabometyx as a key treatment option in a broad range of tumors is continuing to be realized.
Press Release - ExelixisCABOMETYX reduced the risk of disease progression or death by 81% versus placebo in patients with advanced lung or thymic neuroendocrine ...
Study Details | NCT01866410 | Cabozantinib-S-Malate and ...Giving cabozantinib-s-malate together with erlotinib hydrochloride may be an effective treatment for non-small cell lung cancer. Detailed Description.
CONTACT-01: A Randomized Phase III Trial of ...To evaluate the efficacy and safety of atezolizumab plus cabozantinib versus docetaxel in patients with metastatic non–small cell lung cancer ( ...
Management of Adverse Events Associated with ...This review reports on the safety profile of cabozantinib in patients with advanced renal cell carcinoma and offers guidance on the management of adverse ...
Cabometyx, INN-Cabozantinib - EMADescription of selected adverse reactions. Data for the following reactions are based on patients who received CABOMETYX 60 mg orally once daily as monotherapy ...
Cabozantin (Cabometyx®, Cometriq®)Cabozantinib (Cabometyx) carries three FDA approved indications and is used in the treatment of advanced renal cell carcinoma (RCC) with, or without, nivolumab ...
NCT01639508 | Cabozantinib in Patients With RET Fusion- ...The purpose of this phase II study is to find out what effects cabozantinib (XL184) has, good and/or bad, in patients whose tumors one of the following gene ...
Exelixis Provides Update on Phase 3 CONTACT-01 Trial ...Exelixis Provides Update on Phase 3 CONTACT-01 Trial Evaluating Cabozantinib in Combination with Atezolizumab in Patients with Metastatic Non-Small Cell Lung ...
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