Lapatinib + Paclitaxel for Ovarian Cancer

Overseen By Frederick Ueland, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Frederick R. Ueland, M.D.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Hypersensitivity, Uncontrolled illness, Malabsorption, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of two drugs, lapatinib (a targeted therapy) and paclitaxel (a chemotherapy drug), for treating ovarian cancer that has not responded to standard platinum-based chemotherapy. Researchers seek to assess the safety of these drugs when used together and identify the best dose for future studies. Candidates may qualify if ovarian cancer returned within a year after platinum chemotherapy and they can manage daily activities with little assistance. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing an opportunity to be among the first to receive this new combination therapy.

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

The trial requires that you do not take medications that affect CYP3A4, which is a liver enzyme that processes drugs. If you're on such medications, you may need to stop them, but the protocol doesn't specify a general requirement to stop all current medications.

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

Research has shown that the combination of lapatinib and paclitaxel appears promising. In one study with 12 patients, two experienced partial tumor shrinkage, and one had stable disease, meaning their tumor did not grow for a while.

Another study found that these drugs helped delay the worsening of a specific type of cancer and improved overall response rates.

While these results are encouraging, they indicate that the treatment remains in early testing stages. Researchers are still studying its safety and patient tolerance. Early-phase trials typically focus on finding the best dose and checking for side effects.

Thus, while some evidence suggests that lapatinib and paclitaxel can work together, the complete safety profile in humans is still being determined. Participants should be aware of this ongoing research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Lapatinib and Paclitaxel for ovarian cancer because it offers a unique approach compared to standard treatments like carboplatin and paclitaxel alone. Lapatinib is a targeted therapy that specifically inhibits certain proteins involved in cancer cell growth, which could enhance the effectiveness of Paclitaxel, a chemotherapy drug. By combining these two, there's potential to improve outcomes by more effectively targeting cancer cells and possibly reducing resistance to treatment. This dual-action approach could provide a new avenue for patients who might not respond as well to existing therapies.

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

Research has shown that using lapatinib and paclitaxel together may help treat ovarian cancer. In one study, about 16% of patients experienced significant tumor shrinkage. Another study found a 44% overall response rate, with some patients experiencing complete tumor disappearance. This trial will test different dosages of lapatinib combined with paclitaxel to evaluate their effectiveness for patients whose cancer does not respond to platinum-based treatments. These early results suggest potential benefits for those with difficult-to-treat ovarian cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Frederick R. Ueland

Principal Investigator

Markey Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with ovarian cancer that came back within a year after platinum-based chemo. They should be fairly active (ECOG ≤2), have good organ and bone marrow function, and able to consent. It's not for those allergic to the drugs being tested, with uncontrolled sickness, heart failure, trouble absorbing food, taking certain other meds or any experimental cancer treatments.

Inclusion Criteria

My organs and bone marrow are working well.

I can take care of myself and am up and about more than half of my waking hours.

My ovarian cancer returned within a year after platinum chemotherapy.

Exclusion Criteria

I am not allergic to lapatinib or paclitaxel.

I am taking medication that affects liver enzyme CYP3A4.

I have been diagnosed with congestive heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dose-escalation of Lapatinib and Paclitaxel to establish the phase II dose

4 weeks

Visits on days 1, 8, and 15

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Lapatinib
• Paclitaxel

Trial Overview The study tests increasing doses of Lapatinib combined with Paclitaxel in patients whose ovarian cancer resisted platinum chemotherapy. The goal is to find the safest dose level that can be used in future phase II trials.

How Is the Trial Designed?

Group I: Lapatinib - Group 3 Experimental Treatment 1 Intervention

Patients in this group will receive Lapatinib (2000mg PO BID) and Paclitaxel (80mg/m2).

Group II: Lapatinib - Group 2 Experimental Treatment 1 Intervention

Patients in this group will receive Lapatinib (1500mg PO BID) and Paclitaxel (80mg/m2).

Group III: Lapatinib - Group 1 Experimental Treatment 1 Intervention

Patients in this group will receive Lapatinib (750mg PO BID) and Paclitaxel (80mg/m2).

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

Approved in United States as Tykerb for:

• Advanced or metastatic breast cancer in combination with capecitabine for patients whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab

Approved in European Union as Tyverb for:

• Advanced or metastatic breast cancer in combination with capecitabine for patients whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab

Who Is Running the Clinical Trial?

Frederick R. Ueland, M.D.

Lead Sponsor

Trials

6

Recruited

850+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04608409

Dose Escalation of Lapatinib With Paclitaxel in Ovarian ... This trial will be a phase I dose-escalation study of lapatinib and paclitaxel for platinum-resistant ovarian cancer, which will establish the phase II dose for ...

2. research.uky.edu research.uky.edu/news/uk-study-shows-combination-therapy-may-potentially-improve-ovarian-cancer-patient-outcomes

UK Study Shows Combination Therapy May Potentially ... A recent study demonstrates that a combination of two drugs used together provides better than expected results, providing a promising treatment strategy ...

3. aacrjournals.org aacrjournals.org/cancerres/article/84/5_Supplement_2/B021/734629/Abstract-B021-A-phase-1-dose-escalation-study-of

Abstract B021: A phase 1 dose escalation study of lapatinib ... Among the 12 patients evaluable for efficacy, there were two partial responses and one stable disease for an objective response rate of 16% and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12088972/

Ovarian cancer targeted therapy: current landscape and future ... Over 80% of newly diagnosed patients achieve partial or complete remission after initial treatment; however, most experience relapse within three years, and ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S194143901170071X

A Phase I/II Study of Lapatinib Plus Carboplatin and ... The overall response rate of the 25 evaluable patients was 44%, with 4 (16%) complete responses and 7 (28%) partial responses. Nine patients achieved stable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2651098/

Phase III, Double-Blind, Randomized Study Comparing ... In 86 HER-2–positive patients (15%), treatment with paclitaxel-lapatinib resulted in statistically significant improvements in TTP, EFS, ORR, and CBR compared ...