PU-H71 With Nab-paclitaxel (Abraxane) in Metastatic Breast Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT03166085

Collaborator

Samus Therapeutics, Inc. (Industry)

Enrollment

Location

Arm

54.7

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to decide the best dose of the study drug, PU-H71, that can be given in combination with the standard chemotherapy drug, nab-paclitaxel (Abraxane).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: PU-H71 Drug: Nab-paclitaxel	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is an open-label, phase Ib study of PU-H71 plus nab-paclitaxel (Abraxane) in patients with HER2-negative metastatic breast cancer (MBC).This is an open-label, phase Ib study of PU-H71 plus nab-paclitaxel (Abraxane) in patients with HER2-negative metastatic breast cancer (MBC).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Study of PU-H71 With Nab-paclitaxel (Abraxane) in Patients With HER2-Negative Metastatic Breast Cancer

Actual Study Start Date :

May 23, 2017

Actual Primary Completion Date :

Dec 14, 2021

Actual Study Completion Date :

Dec 14, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PU-H71 With Nab-paclitaxel (Abraxane) PU-H71 will be given as an intravenous infusion on Day 1 of a 21 day cycle and nab-paclitaxel will be administered at a dose of 260mg/m2 intravenously on Day 1. Both drugs will be administered on the same day, in sequence, with nab-paclitaxel being administered first followed by administration of PU-H71 as close as possible to 6 hours later (+/-1 hour). PU-H71 will be administered intravenously over a 1 hour period; nab-paclitaxel will be administered per standard guidelines as a 30-minute intravenous infusion.	Drug: PU-H71 PU-H71 will be given as an intravenous infusion on Day 1 of a 21 day cycle Drug: Nab-paclitaxel nab-paclitaxel will be administered at a dose of 260mg/m2 intravenously on Day 1 Other Names: Abraxane

Arm

Intervention/Treatment

Experimental: PU-H71 With Nab-paclitaxel (Abraxane)

PU-H71 will be given as an intravenous infusion on Day 1 of a 21 day cycle and nab-paclitaxel will be administered at a dose of 260mg/m2 intravenously on Day 1. Both drugs will be administered on the same day, in sequence, with nab-paclitaxel being administered first followed by administration of PU-H71 as close as possible to 6 hours later (+/-1 hour). PU-H71 will be administered intravenously over a 1 hour period; nab-paclitaxel will be administered per standard guidelines as a 30-minute intravenous infusion.

Drug: PU-H71

PU-H71 will be given as an intravenous infusion on Day 1 of a 21 day cycle

Drug: Nab-paclitaxel

nab-paclitaxel will be administered at a dose of 260mg/m2 intravenously on Day 1

Other Names:

Abraxane

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) [1 year]
The MTD will be the dose level at which 0/6 or 1/6 patients experience excessive toxicity with the next higher dose having at least 2/3 or 2/6 patients experiencing excessive toxicity. This means that if only 3 patients have been treated at a particular dose level and none of them had excessive toxicity, another 3 patients will be treated to verify that no more than 1 out of 6 patients had excessive toxicity.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years or older
Signed informed consent
Patients must have histologically confirmed HER2-negative breast cancer (defined as IHC 0 or 1+ and/or fluorescence in situ hybridization [FISH] < 2.0), that is metastatic in stage
For estrogen receptor (ER)-positive breast cancer, patients must be considered refractory to endocrine therapy, having received and progressed through at least one prior line of endocrine therapy, or are intolerant of endocrine therapy
All patients must have progressed on at least one line of cytotoxic therapy for metastatic disease
Patients must have evidence of progressive disease
Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Hematologic parameters: white blood cell (WBC) count of ≥ 3000/ul, absolute neutrophil count (ANC) ≥ 1500/ul, platelets ≥ 100,000/ul, hemoglobin ≥ 9.0 g/dl
Non-hematologic parameters: bilirubin ≤ 1.5 mg/dl, AST/ALT ≤ 3.0 x upper limit of normal (ULN) (≤ 5.0 x ULN if liver metastases are involved)
Serum creatinine < 1.5 xULN or CrCl > 40 mL/min (measured or calculated using the Cockcroft-Gault formula)
An Eastern Cooperative Oncology Group performance status of 0-2
Life expectancy of 3 months or more as assessed by the investigator
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause.
Women of childbearing potential must agree and commit to the use of a highly effective method of contraception. Men must agree and commit to use a barrier method of contraception while on treatment and for 3 months after last dose of investigational products.

Exclusion Criteria:

Symptomatic brain or CNS metastases. Previously treated and stable CNS disease is allowed.
Any of the following for the treatment of cancer within 2 weeks of first study treatment: chemotherapy, immunotherapy, experimental therapy, or biologic therapy.
Radiation therapy (other than palliative radiation to bony metastases) as cancer therapy within 4 weeks prior to initiation of study treatment
Any major surgical procedure within 4 weeks of first study treatment
Prior treatment with Abraxane
Active liver disease, including viral or other hepatitis, or cirrhosis
Pregnancy or lactation
Other active infections aside from hepatitis
Any other significant medical condition not under control, including any acute coronary syndrome within the past 6 months.
Patients with a permanent pacemaker
Patients with a QTc > 480 ms in the baseline EKG
Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable/evaluable disease
Peripheral neuropathy of grade ≥ 2 per NCI CTCAE, Version 4.0, at the time of or within 3 weeks prior to the first study therapy
Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results in the judgment of the investigator
History of an invasive second primary malignancy diagnosed within the previous 3 years, except for appropriately treated stage I endometrial or cervical carcinoma or prostate carcinoma treated surgically, and non-melanoma skin cancer.