Cyclophosphamide + Veliparib for Advanced Breast Cancer

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticonvulsants, Antiretrovirals

Disqualifiers: Active infection, Seizure disorder, 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, up to 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs, cyclophosphamide (also known as Cytoxan, Neosar, or Endoxan) and veliparib, to evaluate their effectiveness in treating advanced breast cancer that has spread. The researchers aim to determine the best dose and identify any side effects. This trial may suit individuals with HER2-negative breast cancer that has progressed after previous treatments. Participants should have prior experience with chemotherapy for metastatic disease and be able to swallow capsules. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are on other investigational drugs or have not recovered from side effects of previous treatments. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combining cyclophosphamide and veliparib is generally well-tolerated by patients with advanced cancer. In a previous study, patients took both medications and experienced mostly manageable side effects. The most common issues included low blood cell counts, tiredness, and nausea, but these were not severe for most individuals.

Another study found similar results, indicating that the combination was safe enough to recommend a dose. Patients did not experience unexpected or severe reactions. This suggests that while some side effects may occur, the treatment is mostly safe. It is important to consult a healthcare provider to understand the risks and benefits for your specific situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Cyclophosphamide and Veliparib for advanced breast cancer because they offer a novel approach to treatment. Unlike the standard therapies, which mainly involve hormone treatments or traditional chemotherapy, Veliparib is a PARP inhibitor that targets cancer cells' ability to repair DNA, potentially leading to more effective tumor reduction. Cyclophosphamide, a proven chemotherapy agent, complements this by directly damaging cancer cell DNA. Together, these drugs may enhance treatment efficacy and overcome resistance seen with current options, offering new hope for patients with advanced stages of breast cancer.

What evidence suggests that cyclophosphamide and veliparib might be an effective treatment for advanced breast cancer?

Research has shown that cyclophosphamide, a well-known chemotherapy drug, kills cancer cells or stops their growth. Veliparib may inhibit cancer cell growth by blocking certain necessary enzymes. This trial will study the combination of these two drugs, as some studies suggest that using them together might be more effective for treating advanced breast cancer. However, other research found that adding veliparib to cyclophosphamide did not significantly improve results compared to cyclophosphamide alone. While this combination is promising due to the potential synergy of the drugs, more research is needed to confirm its effectiveness for breast cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Joseph Sparano, MD

Principal Investigator

Montefiore Medical Center - Moses Campus

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic HER2/neu negative breast cancer who've had prior chemotherapy. They must have a certain level of blood cells, no severe liver/kidney issues, and be able to take oral meds. Pregnant women, those unable to use contraception, or patients with recent seizures or bowel obstructions can't join.

Inclusion Criteria

My cancer is not HER2 positive, as tested on my primary or metastatic tumor.

Your platelet count is at least 100,000 per microliter.

I've had chemotherapy for my cancer, or I have a BRCA1 or BRCA2 mutation.

Exclusion Criteria

Patients may not be receiving any other investigational agents

I have previously been treated with PARP inhibitors like veliparib or olaparib.

I haven't had radiotherapy in the last 3 weeks or recovered from previous treatment side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive veliparib and cyclophosphamide orally once daily on days 1-21, with courses repeating every 21 days in the absence of disease progression or unacceptable toxicity

21 days per cycle, up to 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Veliparib

Trial Overview The study tests the combination of Cyclophosphamide (a chemo drug) and Veliparib (which blocks enzymes helping tumor growth) in treating advanced breast cancer. It aims to find the safest doses and observe side effects when these drugs are given together.

How Is the Trial Designed?

Group I: Treatment (veliparib, cyclophosphamide) Experimental Treatment 3 Interventions

Patients receive veliparib orally PO QD and cyclophosphamide PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

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

Epirubicin, which has lower cardiotoxicity than doxorubicin, allows for higher cumulative doses and is effective in treating metastatic breast cancer, making it a safer option for patients.

A phase III trial is set to compare the effectiveness of a concurrent epirubicin/taxane regimen against a sequential epirubicin/cyclophosphamide followed by taxane treatment in patients with operable node-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of a phase III trial of adjuvant sequential epirubicin/ cyclophosphamide and taxane versus concurrent epirubicin/taxane in operable node-positive breast cancer. Perez, EA.[2019]

In a study involving 66 patients with androgen-independent prostate carcinoma, the combination of weekly paclitaxel and estramustine phosphate led to a 42% rate of prostate-specific antigen (PSA) decline, indicating significant efficacy in managing the disease.

The treatment was generally well tolerated, with low rates of severe toxicities; however, there was one treatment-related death, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase II study of estramustine phosphate plus weekly paclitaxel in patients with androgen-independent prostate carcinoma. Vaughn, DJ., Brown, AW., Harker, WG., et al.[2015]

In a phase II study involving 44 patients with metastatic breast cancer, the combination of capecitabine and paclitaxel (XP) showed an overall response rate of 46.5%, indicating significant antitumor activity.

The treatment was well-tolerated, with manageable side effects, and resulted in a progression-free survival of 8.3 months and overall survival of 22.9 months, making it a viable option for patients with limited prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose capecitabine plus weekly paclitaxel in patients with metastatic breast cancer: a multicenter phase II study KBCSG-0609. Taguchi, T., Yamamoto, D., Masuda, N., et al.[2015]

In a study of 27 patients with advanced breast cancer who were resistant to previous treatments, the combination of VP 16-213 and cyclophosphamide resulted in a 15% complete response rate and a 26% partial response rate, indicating its efficacy in difficult-to-treat cases.

Despite its effectiveness, the treatment was associated with significant side effects, including gastrointestinal toxicity in all patients and bone marrow toxicity in 81%, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VP16-213 and cyclophosphamide in advanced breast cancer. A phase II study. Estapé, J., Cirera, L., Millá, A., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01351909?term=Cyclophosphamide%20AND%20it%20by&viewType=Table&checkSpell=&rank=9

Cyclophosphamide and Veliparib in Treating Patients With ... Most clinical studies have one primary outcome measure, but some have more than one. ... The main reason for the clinical trial. The types of primary purpose are: ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4860030/

Randomized Phase II trial of Cyclophosphamide and ... The addition of veliparib to cyclophosphamide, at the dose and schedule evaluated, did not improve the response rate over cyclophosphamide treatment alone in ...

3. clinicaltrial.be clinicaltrial.be/en/details/76983?per_page=100&only_recruiting=0&only_eligible=0

Cyclophosphamide and Veliparib in Treating Patients With... Patients receive veliparib orally (PO) once daily (QD) and cyclophosphamide PO QD on days 1-21. Courses repeat every 21 days in the absence of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8934569/

A phase I study of veliparib with cyclophosphamide and ... This phase I trial evaluated the tolerability, safety, and PK of veliparib in combination with iv cyclophosphamide in patients with advanced solid tumors and ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/18/6/1726/190064/A-Phase-I-Study-of-Veliparib-in-Combination-with

A Phase I Study of Veliparib in Combination with Metronomic ... PAR was significantly decreased in PBMCs (by at least 50%) and tumor biopsies (by at least 80%) across dose levels (DL); γH2AX levels were increased in CTCs ...