Copanlisib + Fulvestrant for Hormone Receptor-Positive Cancers

Overseen By Timothy Yap, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inducers, Warfarin

Disqualifiers: CNS involvement, HER2 positive, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments: copanlisib (a PI3K inhibitor) and fulvestrant (also known as Faslodex, a hormone therapy). The aim is to evaluate their combined effectiveness against certain advanced cancers with hormone receptors and specific genetic changes. The focus includes cancers such as ovarian, endometrial, and breast cancer, which involve changes in the PI3K pathway affecting cancer growth. Individuals diagnosed with one of these advanced cancers and possessing specific genetic changes in their tumors might be suitable candidates for this study. The goal is to determine if this combination treatment can effectively target and manage these cancer types. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot use certain strong enzyme inducers or inhibitors from 14 days before starting the study. It's best to discuss your current medications with the study team.

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

Research shows that combining copanlisib and fulvestrant holds promise for patients with advanced breast cancer. Studies have found this combination to be generally safe and well-tolerated. Several trials have tested its effectiveness and safety for these patients.

In earlier studies, patients taking copanlisib with fulvestrant experienced side effects that were usually mild to moderate, such as fatigue or nausea. More serious side effects were less common but did occur. Each person's experience can differ.

The study's later phase indicates that researchers have gathered more information about its safety, suggesting confidence in testing it on more people. It's always advisable to ask the study team any questions about potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for hormone receptor-positive cancers?

Researchers are excited about the combination of copanlisib and fulvestrant because of its novel approach to treating hormone receptor-positive cancers. While standard treatments often focus solely on blocking hormones, copanlisib works differently by targeting the PI3K pathway, which is crucial for cancer cell growth and survival. This dual-action strategy not only potentially enhances the effectiveness of fulvestrant but also offers a new avenue for patients who may not respond well to existing hormone therapies. This innovative mechanism and potential for improved outcomes make this combination a promising option for those battling this type of cancer.

What evidence suggests that copanlisib and fulvestrant could be effective for hormone receptor-positive cancers?

This trial will evaluate the combination of copanlisib and fulvestrant for treating advanced hormone receptor-positive cancers. Research shows that this combination may effectively treat these cancers. Fulvestrant blocks estrogen, which many tumors need to grow, while copanlisib inhibits a pathway cancer cells often use to survive and multiply. Previous studies have demonstrated that this combination can help control tumor growth, particularly in tumors with changes in the PI3K pathway. Overall, the combination has shown promising results in controlling tumor progression. ^{3 6 7 8 9}

Who Is on the Research Team?

Timothy Yap

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced hormone receptor-positive solid tumors, including ovarian, endometrial, or breast cancer. Participants must have specific genetic alterations in the PI3K pathway and no available standard therapy that prolongs survival. They should be healthy enough to follow the study protocol and not pregnant or breastfeeding. Men must use barrier contraception.

Inclusion Criteria

My cancer is ER+ or PR+ and has spread beyond its original site.

I am able to get out of my bed or chair and move around.

There are no standard treatments left that can extend my life.

Exclusion Criteria

I have another cancer that is getting worse or needs treatment.

It's been over 4 weeks or 5 half-lives since my last chemotherapy or experimental treatment.

I am currently being treated for active hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Confirmation

Evaluate the safety, tolerability, and dose-limiting toxicities of copanlisib in combination with fulvestrant to confirm the recommended phase 2 doses

4 weeks

3 visits (in-person) for copanlisib administration, 2 visits (in-person) for fulvestrant administration

Dose Expansion

Assess the efficacy of copanlisib in combination with fulvestrant in 3 indication-specific cohorts

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Copanlisib
• Fulvestrant

Trial Overview The trial tests the effectiveness and safety of combining copanlisib (a PI3K inhibitor) with fulvestrant in treating cancers that are positive for estrogen/progesterone receptors and have certain genetic changes activating the PI3K pathway.

How Is the Trial Designed?

Group I: Part 2: Dose expansion: Experimental Treatment 2 Interventions

The dose expansion part will enroll in 3 indication-specific cohorts with 13 to 26 patients

Group II: Part 1: Dose confirmation Experimental Treatment 2 Interventions

Up to 6 evaluable patients to confirm a single combination dose of copanlisib and fulvestrant

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

Fulvestrant, an estrogen receptor antagonist, was effective in treating advanced breast cancer in postmenopausal women, showing an overall clinical benefit in 39% of the 339 patients studied, with better outcomes when used as a first-line treatment.

The treatment was well tolerated, with only 5% of patients experiencing adverse events, and it was particularly beneficial for patients with tumors expressing both estrogen and progesterone receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. Steger, GG., Gips, M., Simon, SD., et al.[2018]

In a study involving 451 postmenopausal women with advanced breast cancer, fulvestrant was found to be as effective as anastrozole in terms of time to progression, with median times of 5.5 months for fulvestrant and 5.1 months for anastrozole.

Both treatments were well tolerated, with low withdrawal rates due to adverse events (3.2% for fulvestrant and 1.3% for anastrozole), indicating that fulvestrant is a safe and effective option for patients who have progressed on prior endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. Howell, A., Robertson, JF., Quaresma Albano, J., et al.[2022]

Fulvestrant is an effective estrogen antagonist for postmenopausal women with hormone-sensitive advanced breast cancer, particularly after they have progressed on other antiestrogen therapies, and it has recently been approved at a higher dose of 500 mg/month based on clinical trial results.

While fulvestrant alone is effective, combining it with growth factor signaling inhibitors may enhance its efficacy, and further research is needed to understand resistance mechanisms in patients who still respond to antiestrogen therapy after prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in the management of postmenopausal women with advanced, endocrine-responsive breast cancer. Oakman, C., Moretti, E., Santarpia, L., et al.[2018]

In a phase II study involving 205 postmenopausal women with advanced hormone receptor-positive breast cancer, high-dose fulvestrant (500 mg/month) showed a clinical benefit rate (CBR) similar to anastrozole (72.5% vs. 67.0%), indicating comparable effectiveness as first-line therapy.

Fulvestrant high-dose was associated with a significantly longer time to progression (TTP) compared to anastrozole, suggesting it may provide a more durable response in treatment, while both therapies had similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study. Robertson, JF., Llombart-Cussac, A., Rolski, J., et al.[2022]

In a study of 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

In a study of 402 postmenopausal women with advanced breast cancer receiving fulvestrant through a Compassionate Use Program, 29.9% experienced clinical benefits, including partial responses and stable disease for over 6 months.

Fulvestrant was well tolerated, with only 1.5% of patients discontinuing treatment due to adverse events, indicating its safety and potential as an effective option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. Neven, P., Paridaens, R., Pelgrims, G., et al.[2018]

In a study of 67 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), copanlisib showed an overall objective response rate (ORR) of 19.4%, with a higher response in activated B-cell like (ABC) DLBCL patients (31.6%) compared to germinal center B-cell like (GCB) patients (13.3%).

Copanlisib demonstrated a manageable safety profile, with common adverse events including hypertension (40.3%), diarrhea (37.3%), and hyperglycemia (32.8%), indicating it may be a viable treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma. Lenz, G., Hawkes, E., Verhoef, G., et al.[2021]

In a study of 400 postmenopausal women with advanced breast cancer, fulvestrant was found to be as effective as anastrozole in delaying disease progression, with a median time to progression of 5.4 months for fulvestrant compared to 3.4 months for anastrozole.

Fulvestrant also demonstrated a significantly longer duration of response in patients who responded to treatment, with a median duration of 19.0 months compared to 10.8 months for anastrozole, indicating it may provide a more sustained benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. Osborne, CK., Pippen, J., Jones, SE., et al.[2022]

Citations

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Copanlisib + Fulvestrant for Hormone Receptor-Positive ... The purpose of this study is to evaluate the efficacy and safety of copanlisib in combination with fulvestrant in advanced hormone receptor-positive (HR+) solid ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03939897

NCT03939897 | Testing the Addition of Copanlisib to Usual ... This phase I trial studies the effects (good and bad) of adding copanlisib to the usual therapy of fulvestrant and abemaciclib in treating patients with ...

3. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/copanlisib

Copanlisib - an overview Copanlisib is defined as an intravenous pan-PI3K inhibitor that exhibits potent antitumor and pro-apoptotic activity in various tumor cell lines and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6124791/

Clinical utility of fulvestrant in the treatment of breast cancer Fulvestrant is the first selective estrogen receptor (ER) downregulator available in clinical practice. It is a pure antiestrogen with no ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-09936

Copanlisib and Fulvestrant for the Treatment of Estrogen ... Fulvestrant blocks the use of estrogen by the tumor cells. Giving copanlisib in combination with fulvestrant may help to control advanced solid tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03803761

A Study of a New Drug Combination, Copanlisib and ... Giving copanlisib and fulvestrant may work better in treating patients with ER+ and HER2- breast cancer compared to fulvestrant alone. Detailed Description.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12174159/

Efficacy and safety of PI3K inhibitors combined with ... The combination of PI3K inhibitors and fulvestrant significantly improved PFS and ORR in patients with advanced breast cancer.

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-02752

Testing the Addition of Copanlisib to Usual Treatment ... This phase I trial studies the effects (good and bad) of adding copanlisib to the usual therapy of fulvestrant and abemaciclib in treating patients with ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03377101

Fulvestrant and Palbociclib With or Without Copanlisib in ... This randomized phase II trial studies the side effects and how well fulvestrant and palbociclib with or without copanlisib work in treating patients with ...