BP1001-A + Paclitaxel for Solid Tumors
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Bio-Path Holdings, Inc.
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a phase I, open-label, study of BP1001-A in participants with advanced or recurrent solid tumors. The dose escalation phase will determine the safety and the maximum tolerated dose (MTD) or maximum administered dose (MAD) of BP1001-A as a single agent. After the MTD or MAD of BP1001-A is established, the dose expansion phase will commence and determine the safety, toxicity and response of BP1001-A in combination with paclitaxel.
Do I need to stop my current medications for the trial?
The trial requires that any hormonal therapy directed at the malignant tumor be stopped at least two weeks before starting BP1001-A. Other prior therapies for the tumor must be stopped at least four weeks before the first dose of BP1001-A. Hormone replacement therapy and stable hormonal therapy for prostate, ovarian, or breast cancer can continue.
What data supports the effectiveness of the drug BP1001-A + Paclitaxel for solid tumors?
Paclitaxel, a component of the treatment, has shown effectiveness in treating various advanced or metastatic cancers, including breast, ovarian, and head and neck cancers, even in patients who did not respond to previous treatments.
12345What safety data exists for paclitaxel in humans?
Paclitaxel has been used in cancer treatment and is generally safe with premedication, but it can cause side effects like hypersensitivity reactions, low white blood cell counts (neutropenia), nerve damage (neurotoxicity), and hair loss (alopecia). These side effects are often related to the dose and schedule of the treatment.
678910What makes the drug BP1001-A + Paclitaxel unique for treating solid tumors?
The combination of BP1001-A with Paclitaxel is unique because it potentially offers a novel mechanism of action by combining a new treatment (BP1001-A) with Paclitaxel, a well-established chemotherapy drug known for its ability to stabilize microtubules and treat various cancers. This combination may enhance the effectiveness of treatment for solid tumors by leveraging the strengths of both components.
1112131415Eligibility Criteria
Adults (≥18 years) with advanced or recurrent solid tumors, such as ovarian, endometrial, fallopian tube cancer, who have no other beneficial treatments available. They must be willing to undergo biopsies and have a life expectancy >3 months. Participants need an ECOG score of 0 or 1 and adequate organ function. Women must not be pregnant and agree to birth control; men also need to use contraception.Inclusion Criteria
My cancer can be measured and has a specific area that can be evaluated.
My ovarian cancer is of a specific cell type.
I am 18 or older with advanced cancer and no known beneficial treatment options.
My blood, liver, kidneys, nerves, and clotting functions are all working well.
I have been treated with docetaxel before.
I am fully active or can carry out light work.
I have a specific type of ovarian, peritoneal, fallopian tube, or endometrial cancer and can be treated with paclitaxel alone.
I stopped all cancer treatments, including immunotherapy, at least 4 weeks ago.
I am a woman who can have children, not pregnant, and agree to use birth control.
My endometrial cancer is of a specific cell type.
Exclusion Criteria
I have no lasting side effects worse than mild from previous treatments.
I have HIV with a specific CD4+ T-cell count or active hepatitis B/C.
I have not had major surgery, dental surgery, or biopsy recently.
I have no history of brain-related health issues in the past 6 months.
I have had a bone marrow or stem cell transplant.
I have fluid buildup in my chest that causes symptoms.
I am not pregnant or breastfeeding.
I cannot or should not receive paclitaxel for my condition.
Participant Groups
The trial is testing BP1001-A alone and combined with paclitaxel in patients with certain solid tumors. It's in phase I where they first find the safest dose for BP1001-A by itself, then see how it works together with paclitaxel regarding safety, toxicity response.
2Treatment groups
Experimental Treatment
Group I: BP1001-A monotherapyExperimental Treatment1 Intervention
Dose escalation of BP1001-A monotherapy
Group II: BP1001-A and PaclitaxelExperimental Treatment1 Intervention
Dose expansion of selected dose of BP1001-A with paclitaxel
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Holy Cross HospitalSilver Spring, MD
The University of Texas M.D. Anderson Cancer CenterHouston, TX
Karmanos Cancer InstituteDetroit, MI
Mary Crowley Cancer ResearchDallas, TX
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Who is running the clinical trial?
Bio-Path Holdings, Inc.Lead Sponsor
References
Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer. [2022]Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy.
A Real-World Retrospective Cohort Study of Combined Therapy with Bevacizumab and Paclitaxel in Japanese Patients with Metastatic Breast Cancer. [2022]Combined therapy with bevacizumab and paclitaxel (BP regimen) as a first-line treatment has proven highly effective with good tolerance for patients with metastatic breast cancer (MBC). The objective of this study was to examine the efficacy and safety of the BP regimen for Japanese patients with MBC in real-world clinical settings.
Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]Paclitaxel has shown activity in metastatic breast cancer, including anthracycline-resistant breast cancer. The efficacy, toxicity and optimal scheduling of the combination of the two drugs needs to be defined.
Update on the antitumor activity of paclitaxel in clinical trials. [2017]Paclitaxel is one of the most active new agents introduced in cancer therapy in the last decade. Results from both completed and ongoing Phase II studies provide evidence that paclitaxel is active as salvage therapy in patients with several advanced or metastatic tumor types, including NSCLC, ovarian, breast, and head and neck cancers. The response rates achieved in these tumors are particularly impressive because heavily pretreated patients, and those who are refractory to prior standard chemotherapy, have had a high rate of objective responses to paclitaxel. Ongoing studies should define clearly the role of paclitaxel in ovarian cancer. The role of this agent in breast cancer will be defined when the optimal use of paclitaxel in combination with other drugs is determined. In other cancers, including NSCLC and head and neck cancer, future studies will use combinations of cisplatin and paclitaxel. Use of paclitaxel also is being investigated in bladder, esophageal, and stomach cancers, as well as pediatric malignancies, including leukemias and solid tumors. It will be important to determine if there is a dose-response relationship in the range of dosages currently used clinically. Important unresolved issues in the development of paclitaxel include its role in primary therapy of solid tumors, the optimal length of its infusion, a clearer understanding of the toxicities associated with paclitaxel and the development of methods to prevent or minimize these toxicities, and the efficacy and safety of paclitaxel in combination with other agents.
Salvage treatment with epirubicin and/or paclitaxel in metastatic breast cancer patients relapsed after high-dose chemotherapy with peripheral blood progenitor cells. [2022]To evaluate feasibility and efficacy of paclitaxel as a single agent or in combination with epirubicin in breast cancer taxane-naive patients who have failed previous high-dose chemotherapy.
Paclitaxel in cancer therapy. [2019]The last decade witnessed the introduction of exciting new chemotherapeutic agents. Among these, paclitaxel emerged as one of the most powerful compounds. Paclitaxel promotes the polymerisation of tubulin, thereby causing cell death by disrupting the normal microtubule dynamics required for cell division and vital interphase processes. Mechanisms of acquired resistance to paclitaxel include alterations of tubulin structure and the amplification of membrane phosphoglycoproteins that function as drug-efflux pumps. Toxicities associated with paclitaxel include hypersensitivity reaction, neurotoxicity and haematological toxicities. Toxicities may be both dose- and schedule-dependent. Paclitaxel has activity against a broad band of tumour types, including breast, ovarian, lung, head and neck cancers. Paclitaxel also has activity in other malignancies that are refractory to conventional chemotherapy, including previously-treated lymphoma and small cell lung cancers and oesophageal, gastric endometrial, bladder and germ cell tumours. Paclitaxel is also active against AIDS-associated Kaposi's sarcoma.
Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview. [2015]The paclitaxel represents first agent from novel class of antineoplastic drugs-taxoids. The clinical development of paclitaxel was initially hampered by hypersensitivity reactions. Current dosage regiments with premedication reduced the incidence of these side effects to less than 3%. The major dose-limiting adverse effect of paclitaxel is neutropenia. Significant activities have been reported in patients with advanced ovarian, breast, non-small cell lung cancer (NSCLC) and head and neck cancer. Combination of paclitaxel with platinum in the treatment of patients with advanced ovarian cancer has a potential to become first-line chemotherapy regimen in the treatment of this disease Long-term follow-up will also allow to determine the effect of the drug on patient survival. The promising results of this drug in the treatment of patients with other malignancies need to be confirmed in ongoing clinical studies.
Paclitaxel (Taxol) efficacy in patients with advanced breast cancer resistant to anthracyclines. [2015]We assessed the efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when administered by 3-hour intravenous infusion in 15 patients with advanced breast cancer resistant to anthracyclines. Paclitaxel was administered at 175 mg/m2. In the event of severe toxicity, dose reductions to 150 or 125 mg/m2 could be made; otherwise, the dose was subsequently increased to 200 mg/m2. Patients received a median of five cycles of treatment (range, one to nine cycles). Paclitaxel induced three complete responses and four partial responses, for an overall response rate of 47%. The most frequently observed toxicities associated with paclitaxel administration were neutropenia and alopecia, which occurred in all patients. The frequency and severity of the observed toxicities were never of clinical concern. We conclude that paclitaxel is active in breast cancer patients clinically resistant to anthracyclines and that it can be safely administered by 3-hour infusion with standard premedication. Considering the good tolerability, higher doses of paclitaxel in advanced breast cancer should be explored.
Taxanes: an overview of the pharmacokinetics and pharmacodynamics. [2023]Paclitaxel and docetaxel have emerged in the last two decades as effective antitumor agents in a variety of malignancies. Paclitaxel is a semisynthetic taxane isolated from bark of the Pacific yew tree. Docetaxel is a semisynthetic taxane derived from the needles of the European yew (Taxus baccata). These compounds bind to tubulin, leading to microtubule stabilization, mitotic arrest and, subsequently, cell death. Plasma clearance of paclitaxel exhibits nonlinear kinetics, which results in a disproportionate change in plasma concentration and area under the curve (AUC) with dose alterations. In contrast, docetaxel has a linear disposition over the dose ranges used clinically, so its concentration changes linearly with changes in the dosage. Premedicating with corticosteroids and histamine H1 and H2 receptor antagonists is advocated prior to paclitaxel administration; prior to docetaxel administration, premedication with corticosteroids is suggested. The taxanes are metabolized in the liver by the cytochrome P-450 enzymes and are eliminated in the bile. The known metabolites are either inactive or less potent than the parent compounds. The toxic effects associated with paclitaxel therapy are mainly neutropenia, peripheral neuropathy, and, rarely, cardiotoxicity. Docetaxel toxicity produces mainly myelosuppression and a cumulative dose fluid retention syndrome. Paclitaxel demonstrates sequence-dependent interactions with cisplatin, cyclophosphamide, and doxorubicin. Docetaxel has shown increased myelosuppression with preceding ifosfamide in a preliminary study. The future holds increasing indications for taxanes in newer combination regimens; consideration of their pharmacologic characteristics is an important aspect of designing and applying new taxane-based treatment regimens.
Paclitaxel: a new antineoplastic agent for refractory ovarian cancer. [2015]The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of paclitaxel are reviewed. Paclitaxel is a diterpenoid taxane derivative found in the bark and needles of the western yew, Taxus brevifolia. Although it shares some structural similarities with other natural alkaloids, it contains a unique taxane ring. It is also unique in that its mechanism of action involves interruption of mitosis by promoting and stabilizing microtubule formation. Paclitaxel doses greater than 60 mg/sq m i.v. consistently produce mean peak plasma concentrations of 2-13 microM. Liver metabolism and biliary excretion are probably responsible for most of the drug's elimination. In clinical trials, paclitaxel has shown substantial activity against advanced, refractory ovarian cancer, metastatic breast cancer, and lung cancer. Paclitaxel may slow the course of melanoma and is being investigated in patients with advanced head and neck cancer and gastrointestinal cancer. Neutropenia is the major dose-limiting toxic effect of paclitaxel. Other adverse effects include hypersensitivity reactions, cardiac toxicity, and neurotoxicity. The recommended dosage for the treatment of recurrent metastatic ovarian cancer is 135 mg/sq m i.v. given over 24 hours every three weeks. It is recommended that neutrophil-count and platelet-count recovery be allowed to occur before the next treatment cycle is begun. Paclitaxel's activity against refractory ovarian cancer has not been matched since the inclusion of cisplatin in treatment regimens.
Paclitaxel (Taxol®): A new natural product with major anticancer activity. [2012]Paclitaxel, the first of a new class of microtubule-stabilizing anti-tumor agents, has been hailed as the most significant chemotherapy advance in 15 years. Early clinical results showed response rates of 24%-30% in platinum refractory ovarian cancer at doses ranging from 110-250 mg/m(2) repeated every three to four weeks. The dose limiting toxicity is neutropenia which is characteristically profound, but brief. Severe hypersensitivity reactions which occurred in the phase I studies can be prevented by the use of anti-allergic pre-medication. From a slow start constrained by drug availability, the clinical development of paclitaxel has accelerated dramatically as the issue of product supply has been solved. Substantial activity has been reported in advanced breast cancer (56% RR in pre-treated patients; 62% RR in patients untreated for advanced disease) and non-small cell lung cancer (NSCLC) (20%-30% RR in advanced stage IIIb/IV patients). Significant activity has been reported also in melanoma, small cell lung cancer (SCLC), bladder cancer, squamous cell carcinoma of the head and neck, and of the esophagus, cervical and endometrial cancer, as well as lymphomas. Combination chemotherapy studies have shown high activity in a variety of tumor types. Superiority over standard therapy has been demonstrated in ovarian and lung cancer in phase III randomized studies. Paclitaxel's novel mechanism of action and relative lack of clinical cross-resistance with other agents suggest a role in the combination therapy of early stage disease.
Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxane-pretreated patients. [2022]There is a deep need to improve the care of metastatic breast cancer (MBC) patients, since even today it remains an incurable disease. Taxanes are considered the most effective cytotoxic drugs for the treatment of MBC, both in monotherapy and in combined schedules, but the need for synthetic solvents contributes to the severe toxicities and may have a negative impact on the efficacy. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) is a colloidal suspension of paclitaxel and human serum albumin initially developed to avoid the toxicities associated with conventional taxanes.
Phase I results of a phase I/II study of weekly nab-paclitaxel in paediatric patients with recurrent/refractory solid tumours: A collaboration with innovative therapies for children with cancer. [2019]nab-Paclitaxel has demonstrated efficacy in adults with solid tumours and preclinical activity in paediatric solid tumour models. Results from phase I of a phase I/II study in paediatric patients with recurrent/refractory solid tumours treated with nab-paclitaxel are reported.
The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer. [2015]The first phase II study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in breast cancer was completed at M.D. Anderson Cancer Center, and included 25 patients with metastatic breast cancer who had been previously treated with one chemotherapy regimen. Fourteen of these patients achieved a major objective response; the median response duration was 9 months, and the median survival time, 20 months. Additional trials showed that paclitaxel maintained its antitumor efficacy in patients with two and three prior chemotherapy regimens, including patients with anthracycline-resistant breast cancer. Combination therapy with doxorubicin showed that this combination was effective, although with the long infusion duration used for both agents, sequence-dependent toxic interactions were encountered. In combination with vinorelbine, dose-limiting toxicity included neutropenic fever and neuropathy. High-dose single-agent paclitaxel is currently being explored in the management of inflammatory breast cancer and as part of neoadjuvant chemotherapy for stages II and III operable disease.
Paclitaxel combination therapy in the treatment of metastatic breast cancer: a review. [2015]Combinations of active antineoplastic agents have been the most effective treatment for metastatic breast cancer. Criteria for an effective combination include use of drugs with different mechanisms of action, nonoverlapping toxic effects, and synergistic, or at least additive, antitumor activity. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with its unique mechanism of action, offers an excellent opportunity for development of effective combination therapy against breast cancer. However, a number of problems have hindered the rapid development of effective combinations. The most obvious problem is the lack of a defined optimal dose and schedule of administration. The second problem has been the demonstration of unexpected interactions between paclitaxel and the other component(s) of the combination, often resulting in unusual and serious toxic effects. This review will focus on the phase I and II trials of paclitaxel in combination with established antineoplastic drugs (except doxorubicin and congeners, which is covered elsewhere in this issue) for breast cancer: cisplatin, 5-fluorouracil with or without folinic acid, cyclophosphamide, radiation therapy, as well as novel investigational agents or strategies, edatrexate, monoclonal antibodies to oncogenes, growth factors, and gene therapy with insertion of multidrug resistance gene into blood stem cells. Combination therapy offers exciting possibilities of enhanced antitumor efficacy. However, given the unexpected and serious toxic effects observed, only proven combinations should be used outside the context of a clinical trial. Additionally, the burden of proof will be to show that these combinations have increased antitumor activity, decreased toxicity, or both compared with single-agent paclitaxel.