Ixabepilone + Temsirolimus for Advanced Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Uncontrolled illness, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days per cycle

22 Participants Needed

Trial Summary

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

The trial requires that you stop taking medications that are strong CYP3A4 inducers or inhibitors, unless they can be replaced with another drug. If you're on such medications, you may need to switch to alternatives.

What data supports the effectiveness of the drugs Ixabepilone and Temsirolimus for advanced cancer?

Ixabepilone has shown effectiveness in treating advanced breast cancer, especially in patients whose cancer is resistant to other treatments. It has been used successfully both alone and in combination with other drugs, like capecitabine, to improve outcomes in these patients. ^{1 2 3 4 5}

What is the safety profile of temsirolimus in humans?

Temsirolimus has been studied in various doses and forms, showing common side effects like rash, mouth sores, diarrhea, high blood sugar, and high cholesterol. Serious but rare side effects include lung disease, bowel perforation, and kidney failure. It has been used safely in patients with advanced cancer, but higher doses tend to increase the frequency and severity of side effects. ^{6 7 8 9 10}

How is the drug combination of Ixabepilone and Temsirolimus unique for treating advanced cancer?

The combination of Ixabepilone and Temsirolimus is unique because it pairs a chemotherapy drug (Ixabepilone) with an mTOR inhibitor (Temsirolimus), which may enhance anticancer effects by targeting cancer cells in different ways. This approach is novel compared to standard treatments that typically use single agents. ^{6 8 10 11 12}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of ixabepilone and temsirolimus in treating patients with solid tumors that have spread from the primary site to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ixabepilone together with temsirolimus may kill more tumor cells.

Research Team

Keith C Bible

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with solid tumors that have spread or can't be surgically removed, and who've had no more than two treatments for metastatic disease. They must have adequate blood counts, liver and kidney function, not be pregnant or nursing, able to consent, and willing to use contraception. Excluded are those recently treated with chemotherapy or radiation, with severe heart conditions or other serious illnesses that could affect the study's safety assessment.

Inclusion Criteria

Platelets >= 100,000/mcL

Life expectancy >= 84 days (12 weeks)

My cancer has spread, cannot be surgically removed, and standard treatments have failed.

Exclusion Criteria

Pregnant women

I do not have any severe illnesses that my doctor says are not under control.

My heart condition severely limits my daily activities.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ixabepilone IV over 3 hours on day 1 and temsirolimus IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Ixabepilone
• Temsirolimus

Trial Overview The trial tests the combination of ixabepilone (a chemotherapy drug) and temsirolimus (an enzyme blocker) on patients with advanced solid tumors. It aims to find the safest doses while observing how well these drugs work together in stopping tumor growth by killing cancer cells or preventing them from dividing and spreading.

Participant Groups

Group I: Treatment (ixabepilone, temsirolimus) Experimental Treatment 3 Interventions

Patients receive ixabepilone IV over 3 hours on day 1 and temsirolimus IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Ixabepilone is an effective new chemotherapy option for patients with advanced breast cancer, particularly those with resistant and refractory disease, showing promise both as a standalone treatment and in combination with capecitabine.

Current clinical trials are investigating ixabepilone's potential in various treatment settings, including neoadjuvant and adjuvant therapies, which could expand its use in breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixabepilone as monotherapy or in combination for the treatment of advanced breast cancer. Bertino, EM., Ramaswamy, B.[2021]

Ixabepilone is an effective treatment option for patients with metastatic breast cancer who have not responded to standard chemotherapy, showing clinical activity in those resistant to anthracyclines and taxanes, as demonstrated in Phase II trials.

In a Phase III trial, ixabepilone combined with capecitabine significantly improved objective response rates and progression-free survival compared to capecitabine alone, while being generally well tolerated with manageable side effects like myelosuppression and reversible peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer. Goodin, S.[2019]

In a study involving 63 patients with advanced cancer, temsirolimus was found to be generally well tolerated, with a maximum tolerated dose established at 15 mg/m²/day for heavily pretreated patients and 19 mg/m²/day for minimally pretreated patients.

The treatment showed promising preliminary antitumor activity, with one patient achieving a confirmed partial response lasting 12.7 months, and several others showing stable disease for over 24 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. Hidalgo, M., Buckner, JC., Erlichman, C., et al.[2014]

The maximum tolerated dose of oral temsirolimus for patients with advanced cancer was determined to be 75 mg, with some patients experiencing dose-limiting toxicities such as elevated liver enzymes and rash at higher doses.

Despite some adverse events like mucositis and fatigue, two patients showed minor tumor responses at the 75 mg dose, suggesting potential efficacy that warrants further investigation in metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer. Buckner, JC., Forouzesh, B., Erlichman, C., et al.[2021]

Temsirolimus demonstrated an objective response rate of 9.2% in patients with advanced breast cancer, indicating some level of antitumor activity, particularly in a heavily pretreated population of 109 patients.

The lower dose of 75 mg showed a more tolerable safety profile compared to the higher 250 mg dose, which was associated with increased toxicity, including a notable incidence of grade 3 or 4 depression in 10% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. Chan, S., Scheulen, ME., Johnston, S., et al.[2022]

In a Phase 1 study involving 10 Japanese patients with advanced solid tumors, the maximum-tolerated dose of temsirolimus was determined to be 15 mg/m², with significant toxicities observed at higher doses, including Grade 3 stomatitis and diarrhea.

Temsirolimus demonstrated dose-dependent pharmacokinetics, with peak blood concentrations of both temsirolimus and its active metabolite sirolimus increasing with higher doses, indicating a need for careful dose management in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 clinical study of temsirolimus (CCI-779) in Japanese patients with advanced solid tumors. Fujisaka, Y., Yamada, Y., Yamamoto, N., et al.[2014]

References

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

Ixabepilone as monotherapy or in combination for the treatment of advanced breast cancer. [2021]

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

Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer. [2023]

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

Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Ixabepilone plus capecitabine for Chinese patients with metastatic breast cancer progressing after anthracycline and taxane treatment. [2022]

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

A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. [2014]

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

Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer. [2021]

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

Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

Temsirolimus. [2021]

10. England pubmed.ncbi.nlm.nih.gov

FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma. [2022]

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

A phase I trial of the mTOR inhibitor temsirolimus in combination with capecitabine in patients with advanced malignancies. [2021]

12. England pubmed.ncbi.nlm.nih.gov

A Phase 1 clinical study of temsirolimus (CCI-779) in Japanese patients with advanced solid tumors. [2014]