BP1001-A in Patients With Advanced or Recurrent Solid Tumors

• Status: Not yet recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bio-Path Holdings, Inc.
• Treatments: Albumin-Bound Paclitaxel; Paclitaxel

Criteria

Inclusion Criteria:

1. All participants, ≥ 18 years of age, with histologic proof of advanced or recurrent solid tumors, who are not candidates for known regimens or protocol treatments of higher efficacy or priority

2. Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 or 1

3. Participants must be willing to undergo pre-treatment biopsies. Participants who complete 1 cycle of treatment will undergo post-treatment biopsies. Post-treatment biopsies will be offered to participants who do not complete 1 cycle of treatment

4. For the dose expansion phase, participants must have recurrent or persistent epithelial ovarian, primary peritoneal, fallopian tube or endometrial tumor

5. Endometrial cancer patients with the following histologic epithelial cell types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified, mucinous adenocarcinoma, squamous cell, transitional cell carcinoma, and mesonephric carcinoma. Uterine carcinosarcoma and other sarcomas of the uterus are not eligible.

6. Estimated life expectancy > 3 months in the investigator's opinion

7. All participants must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 10 mm when measured by conventional techniques, including palpitation, plain x-ray, CT, and MRI, or ≥ 10 mm when measured by spiral CT. Measurable disease lesions must be amenable to pre- and post-treatment biopsy

8. Participants must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST v1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

9. Participants must have adequate:

Bone marrow function: Hemoglobin (HgB) > 9 g/dL, White blood cells (WBC) >3,000/mcL, Absolute neutrophil count (ANC) >1,500/mcL, Platelets (PLT) >100,000/mcL Hepatic function: Total bilirubin within normal institutional limits, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) < 2.5 X institutional upper limits of normal (ULN) Renal function: Serum creatinine < 1.5 x ULN or estimated glomerular filtration rate (eGFR) > 60 mL/min according to Cockcroft-Gault formula Neurologic function: Neuropathy (sensory and motor) < CTCAE Grade 1 Blood coagulation parameters: Prothrombin time (PT) such that international normalized ratio (INR) is < 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin or low molecular weight heparin) and a partial thromboplastin time (PTT) < 1.2 times control.

10. Participants previously treated with docetaxel (regardless of response) are eligible for this trial

11. Participants in the dose expansion phase who previously received paclitaxel for primary or recurrent disease are eligible if they did not progress on therapy or relapse within 6 months of completing therapy. Participants with persistent disease at the completion of primary therapy with paclitaxel are not eligible

12. Participants should be free of active infection requiring antibiotics, with the exception of uncomplicated urinary tract infection (UTI)

13. Any hormonal therapy directed at the malignant tumor must be discontinued at least two weeks prior to BP1001-A treatment. Continuation of hormone replacement therapy is permitted; stable regimens of hormonal therapy (i.e. for prostate cancer (e.g. leuprolide, a gonadotropin-releasing hormone [GnRH] agonist), ovarian or breast cancer are not exclusionary

14. Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least four weeks prior to first dose of BP1001-A (6 weeks for nitrosoureas or mitomycin C)

15. Female participants of childbearing potential must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (hCG) performed within 24 hours prior to the start of study treatment. Post-menopausal subjects (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test

16. Female participants of childbearing potential must agree to use an acceptable method of birth control (i.e. a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide or abstinence) for the duration of the study and for at least 6 months after the last dose of treatment

17. Male participants must agree to use an acceptable method of contraception for the duration of the study

18. Participants must be willing and able to provide written informed consent

Exclusion Criteria:

1. For the dose expansion phase, participants must not have low grade serous ovarian carcinoma or mucinous ovarian carcinoma

2. Participants who had previous bone marrow or hematopoietic stem cell transplant

3. Participants who have undergone prior radiation to abdomen and pelvis (if myelosuppression is likely to occur)

4. Participants may not be receiving any other investigational agents

5. Female participants who are pregnant or breast-feeding

6. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)]

7. History or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months of registration on this study

8. Within the past 6 months, participant has had any of the following: myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack

9. Presence of concurrent conditions that, in the opinion of the Investigator and/or Medical Monitor, may compromise the participant's ability to tolerate study treatment or interfere with any aspect of study conduct or interpretation of results. This includes, but is not limited to, unstable or uncontrolled angina, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled and sustained hypertension, clinically significant cardiac dysrhythmia or clinically significant baseline electrocardiogram (ECG) abnormality (e.g., QTcF >470 msec)

10. Active pleural or pericardial effusion of any grade

11. Participants who are ineligible to undergo an MRI scan for reasons such as claustrophobia or the presence of implanted devices or metallic foreign bodies that are not MR compatible, such as ferromagnetic implants or pacers or with a known history of allergic reaction to gadolinium contrast agents

12. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation

13. A prior history of ≥grade 3 hypersensitivity to paclitaxel or docetaxel or with products mixed in Cremephor EL or Tween 80®

14. Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy or procedure, excluding alopecia

15. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

16. Known history of human immunodeficiency virus (HIV) infection or clinically active hepatitis B or C infection

17. Participants who have a major surgical procedure, open biopsy, dental extractions or other dental surgery/procedure that results in an open wound, or significant traumatic injury within 28 days prior to the first date of treatment on this study, or anticipation of need for major surgical procedure during the course of the study; patients with placement of vascular access device or core biopsy within 7 days prior to registration