Cyclophosphamide + Veliparib for Advanced Breast Cancer

Recruiting at 4 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

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of cyclophosphamide and veliparib when given together in treating patients with breast cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Drugs used in chemotherapy, such as cyclophosphamide, 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. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide together with veliparib may work better in treating breast cancer.

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 Cyclophosphamide safe for use in humans?

Cyclophosphamide, also known as Cytoxan or Neosar, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like low blood cell counts and nausea. In some studies, it has been associated with less heart-related side effects compared to other drugs. ^{1 2 3 4 5}

How is the drug combination of Cyclophosphamide and Veliparib unique for advanced breast cancer?

The combination of Cyclophosphamide and Veliparib is unique because it includes Veliparib, a PARP inhibitor (a drug that blocks an enzyme involved in repairing DNA damage in cells), which may enhance the effectiveness of Cyclophosphamide, especially in patients with advanced breast cancer that is resistant to other treatments. ^{1 6 7 8 9}

What data supports the effectiveness of the drug Cyclophosphamide + Veliparib for advanced breast cancer?

Cyclophosphamide, a component of the treatment, has shown promising results in combination with other drugs for advanced breast cancer, improving survival and quality of life. Additionally, new targeted agents like Veliparib have been introduced to enhance outcomes in similar settings. ^{1 8 10 11 12}

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

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]

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

Chemotherapeutic Strategies for advanced breast cancer. [2007]

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

Sequential dose-dense adjuvant therapy with doxorubicin, paclitaxel, and cyclophosphamide. [2015]

3. Germany pubmed.ncbi.nlm.nih.gov

Low dose capecitabine plus weekly paclitaxel in patients with metastatic breast cancer: a multicenter phase II study KBCSG-0609. [2015]

4. Germany pubmed.ncbi.nlm.nih.gov

[Current status in the treatment of breast cancer. II. Adjuvant chemotherapy, palliative polychemotherapy, chemoimmunotherapy--rating and results (author's transl)]. [2019]

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

High-dose cisplatin, etoposide, and cyclophosphamide with autologous stem cell reinfusion in patients with responsive metastatic or high-risk primary breast cancer. [2019]

6. United States 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. [2019]

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

Multicenter Phase II study of estramustine phosphate plus weekly paclitaxel in patients with androgen-independent prostate carcinoma. [2015]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Pathological and clinical response of a primary chemotherapy regimen combining vinorelbine, epirubicin, and paclitaxel as neoadjuvant treatment in patients with operable breast cancer. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

VP16-213 and cyclophosphamide in advanced breast cancer. A phase II study. [2019]

11. Italy pubmed.ncbi.nlm.nih.gov

Etoposide (VP-16-213) and cis-dichlorodiammineplatinum (DDP) in advanced breast carcinoma resistant to previous chemotherapy. [2015]

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

Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. [2022]