Ixabepilone + Temsirolimus for Advanced Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of combining two drugs, ixabepilone and temsirolimus, to determine the optimal dose for treating advanced cancers that have spread or cannot be surgically removed. Ixabepilone, a chemotherapy drug, fights cancer by stopping tumor cells from dividing or spreading, while temsirolimus (also known as Torisel) blocks enzymes necessary for tumor growth. The trial aims to determine if using both drugs together can more effectively kill cancer cells. It is suitable for patients with solid tumors that no longer respond to standard treatments and have already tried up to two other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients a chance to be among the first to receive this novel combination therapy.

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.

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

Research has shown that using ixabepilone and temsirolimus together is safe for patients with advanced cancer. In previous studies, patients tolerated this combination well, though some experienced serious but rare side effects, such as lung disease, a hole in the intestine, and kidney failure.

Most patients responded well to the treatment. Ixabepilone tends to avoid some common side effects of similar drugs, such as muscle and joint pain. Temsirolimus has also generally been well tolerated by patients with certain cancers. This is encouraging for those considering joining a trial for this treatment combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ixabepilone and temsirolimus for advanced cancer because it offers a novel approach compared to standard treatments. Ixabepilone, a microtubule inhibitor, disrupts cancer cell division in a way that differs from traditional chemotherapy drugs. Meanwhile, temsirolimus inhibits a protein called mTOR, which is crucial for cancer cell growth and survival. Together, they target cancer cells through different mechanisms, potentially enhancing treatment effectiveness and overcoming resistance seen with conventional therapies.

What evidence suggests that ixabepilone and temsirolimus might be an effective treatment for advanced cancer?

In this trial, participants will receive a combination of ixabepilone and temsirolimus. Studies have shown that ixabepilone, when combined with other drugs like capecitabine, can significantly improve patient response to treatment and slow cancer spread. Temsirolimus blocks the enzymes necessary for cancer cell growth. This method has benefited patients with various advanced solid tumors. Together, ixabepilone and temsirolimus might be more effective because ixabepilone prevents cancer cells from dividing, while temsirolimus blocks growth signals. Early results suggest this combination could be particularly beneficial for cancers that have spread or cannot be surgically removed. ^{2 3 6 7 8}

Who Is on the Research Team?

Keith C Bible

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 INR level is between 2.0 and 3.0 while on warfarin.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01375829

Ixabepilone and Temsirolimus in Treating Patients With ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3744018/

Preclinical evaluation of the mTOR inhibitor, temsirolimus ... Two recent clinical trials evaluating ixabepilone in metastatic RCC have shown clinical benefit including objective responses and prolonged disease ...

3. withpower.com withpower.com/trial/ixabepilone-temsirolimus-for-advanced-cancer-fca50

Ixabepilone + Temsirolimus for Advanced Cancer In a Phase III trial, ixabepilone combined with capecitabine significantly improved objective response rates and progression-free survival compared to ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7598629/

Small-Molecule Inhibitors (SMIs) as an Effective Therapeutic ... Ridaforolimus treatment was discontinued as a result of adverse events in 33% of patients compared to 6% in the progestin or chemotherapy group.

5. researchgate.net researchgate.net/publication/343865657_Phase_I_study_of_temsirolimus_CCI-779_carboplatin_and_paclitaxel_in_patients_pts_with_advanced_solid_tumors_NCIC_CTG_IND_179

Phase I study of temsirolimus (CCI-779), carboplatin, and ... The regimen is active: of the 26 patients with follow-up data, there have been 10 with partial response (38.5%; med. duration 7.1 mo [1.0–12.7]) and 12 with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01375829

Study Details | Ixabepilone and Temsirolimus in Treating ... 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 ...

7. sciencedirect.com sciencedirect.com/topics/neuroscience/temsirolimus

Temsirolimus - an overview | ScienceDirect Topics In patients with advanced RCC, CCI-779 showed antitumor activity, encouraging survival, and generally was well tolerated over the three dose levels tested.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3811044/

A phase I/II trial and pharmacokinetic study of ixabepilone ... These preclinical data suggest that some adverse reactions seen with paclitaxel such as myalgias and arthralgias might not occur with ixabepilone. Unlike ...