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A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects With Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05261269
Recruitment Status : Recruiting
First Posted : March 2, 2022
Last Update Posted : October 19, 2022
Sponsor:
Information provided by (Responsible Party):
Dantari, Inc.

Brief Summary:

This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and PK of IV administered DAN-222 followed by a dose-escalation of DAN-222 in combination with niraparib. There are two stages within this study:

Stage 1:

  • Part A is dose escalation of single agent DAN-222
  • Part B is dose escalation of DAN-222 in combination with niraparib

Stage 2:

Expansion of three separate HER2-negative mBC cohorts: one group for single agent DAN-222 in subjects with HRD-positive or HRD-negative tumors and 1 cohort each for DAN-222 combined with niraparib of HRD-positive tumors or HRD-negative tumors.


Condition or disease Intervention/treatment Phase
HER2-negative Metastatic Breast Cancer Drug: DAN-222 Drug: Niraparib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects With Metastatic Breast Cancer
Actual Study Start Date : February 2, 2022
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : April 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Niraparib

Arm Intervention/treatment
Experimental: Dose Escalation (DAN-222)
The starting dose of DAN-222 will be administered IV every week (QW) to subjects in the first cohort.
Drug: DAN-222
Administered IV every week to subjects

Experimental: Dose Escalation (DAN-222 + niraparib)
The starting dose of DAN-222 will be administered IV every week (QW), in combination with daily oral niraparib.
Drug: DAN-222
Administered IV every week to subjects

Drug: Niraparib
Administered orally once daily

Experimental: Dose Expansion (DAN-222)
Single agent DAN-222 in HRD-positive or HRD-negative tumors.
Drug: DAN-222
Dose level to be determined based on Stage 1: Dose escalation data. Dose will be administered via IV every week to subjects

Experimental: Dose Expansion (DAN-222 + niraparib, HRD-positive)
Combination DAN-222 with niraparib in HRD-positive tumors.
Drug: DAN-222
Dose level to be determined based on Stage 1: Dose escalation data. Dose will be administered via IV every week to subjects

Drug: Niraparib
Administered orally once daily

Experimental: Dose Expansion (DAN-222 + niraparib, HRD-negative)
Combination DAN-222 with niraparib HRD-negative tumors.
Drug: DAN-222
Dose level to be determined based on Stage 1: Dose escalation data. Dose will be administered via IV every week to subjects

Drug: Niraparib
Administered orally once daily




Primary Outcome Measures :
  1. Incidence and nature of Dose Limiting Toxicities (DLTs) [ Time Frame: 3 years ]
  2. Incidence, nature, and severity of adverse events graded according to NCI CTCAE v5.0 [ Time Frame: 3 years ]
  3. Total exposure (area under the curve) from time 0 to the last measurable concentration (AUC0-last) [ Time Frame: 3 years ]
  4. Maximum observed plasma concentration (Cmax) [ Time Frame: 3 years ]
  5. Minimum observed plasma concentration (Cmin through concentration) [ Time Frame: 3 years ]
  6. Terminal half-life (t1/2) [ Time Frame: 3 years ]
  7. Clearance rate [ Time Frame: 3 years ]
  8. Volume of distribution [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Objective response per RECIST v1.1, defined as the proportion of patients having a best overall response (BOR) of complete response (CR) or partial response (PR), as determined by Investigator review. [ Time Frame: 3 years ]
  2. Progression-free survival per RECIST v1.1, defined as the time from randomization to documented disease progression or death from any cause, whichever occurs earlier as determined by Investigator review. [ Time Frame: 3 years ]
  3. Disease control rate (DCR) per RECIST v1.1, defined as best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by Investigator review. [ Time Frame: 3 years ]
  4. Clinical benefit rate (CBR) per RECIST v1.1, defined as the proportion of patients having a BOR of SD ≥ 6 months, PR or CR as determined by Investigator review. [ Time Frame: 3 years ]
  5. Duration of response, defined as the time from first occurrence of a documented objective response until the time of disease progression, as determined by Investigator review with use of RECIST v1.1, or death from any cause during the study. [ Time Frame: 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects must have histologically documented, metastatic, HER2-negative breast cancer that has progressed after two prior lines of therapy (including adjuvant therapy if progressed within the last 12 months, and aromatase inhibitors will be considered a line of therapy). Subjects with HR+ disease can have prior CDK4/6 inhibitors and subjects with BRCAm disease may have prior PARPi therapy. HER2 positivity is defined by standard of care fluorescence in situ hybridization (FISH) and/or 3+ staining by immunohistochemistory (IHC) according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) Clinical Practice Guideline Focused Update.
  2. A minimum of 2 weeks or 5 half-lives (whichever is longer) will be required from any prior therapy for mBC, including chemotherapy, immunotherapy and/or radiation therapy.
  3. Subjects must have measurable disease as per RECIST v1.1.
  4. Females, age 18 years or older.
  5. ECOG performance status ≤ 2.
  6. Subjects with previously treated brain metastases (surgery, whole or stereotactic brain radiation) are allowed provided the lesions have been stable for at least 4 weeks and the subject is off steroids for at least 7 days prior to first dose of study treatment, and any neurologic symptoms have returned to baseline (without evidence of progression by imaging using the identical imaging modality for each assessment, either MRI or CT scan).
  7. Subjects with brain metastases should not require use of enzyme-inducing antiepileptic drugs (eg, carbamazepine, phenytoin, or phenobarbital) within 14 days before first dose of study treatment and during study. Use of newer antiepileptics that do not produce enzyme induction drug-drug interactions is allowed.
  8. Subjects must have normal organ and marrow function as defined below:

    • absolute neutrophil count ≥ 1.5 x 109/L without growth factor support in the last 7 days
    • platelets ≥ 100 x 109/L without growth factor support in the last 7 days
    • hemoglobin ≥ 9 g/dL and no blood transfusion within 4 weeks
    • total bilirubin ≤ 1.5 x the upper limit of normal (ULN) (unless Gilbert's Disease)
    • AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)
    • creatinine clearance ≥ 60 mL/min (calculated using the Cockroft-Gault formula) for subjects with creatinine levels above institutional normal
  9. Patients of childbearing potential have a negative serum pregnancy test within 72 hours prior to the first dose of study medication. Non-childbearing potential is defined as (by other than medical reasons):

    • 45 years of age or older and has not had menses for > 1 year
    • Amenorrheic at least 2 years without a hysterectomy and oophorectomy and a follicle stimulating hormone (FSH) value in the postmenopausal range upon pre-study (screening) evaluation
    • Post hysterectomy, bilateral oophorectomy, or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the subject must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 120 days after the last dose of study therapy.
  10. Subject is willing and able to comply with the protocol for the duration of the study including providing medical information, study examinations or tests at scheduled visits and study treatment.

    Additional Inclusion Criteria for Stage 2:

  11. Documentation of DNA repair defects status validated from HRD plasma testing through the central laboratory or from archival tumor tissue or germ line testing. This testing will need to occur prior to enrollment.

Exclusion Criteria:

  1. Any significant medical condition or laboratory abnormalities which place the subject at unacceptable risk if he/she were to participate in the study at clinician's discretion and not otherwise stated below.
  2. For the DAN-222 and niraparib combination cohorts, subjects cannot have known sensitivity to FD&C Yellow No. 5 (tartrazine).
  3. Allergic reaction to irinotecan, topotecan, or govitecan.
  4. Concurrent administration or received cytochrome P450 3A4 (CYP3A4) enzyme inducers or inhibitors within 2 weeks prior to the first day of study treatment.
  5. Subjects taking medications know to prolong the QT interval or associated with torsades de pointes, unless the subject can safely discontinue these medications or change to comparable medications that do not significantly prolong the QT interval, at least 5 half-lives or 7 days (whichever is longer) prior to the first dose of DAN-222.
  6. History of myelodysplasia, or has a known additional malignancy that progressed or required active treatment within the last 3 years. Exceptions include non-melanoma skin cancer and carcinoma in situ.
  7. Carcinomatous meningitis.
  8. Subject is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
  9. Inability to comply with study procedures or unwilling to use adequate birth control.
  10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia that would limit compliance with study requirements.
  11. Subject has a heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening.
  12. Any serious social, psychosocial, or medical condition or abnormality in clinical laboratory tests that, in the Investigator's judgment, precludes the subject's safe participation in and through a minimum of 4 cycles of treatment, or which could affect compliance with the protocol or interpretation of results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05261269


Contacts
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Contact: Timothy Hagerty, Ph.D. Please contact via email. clinical@dantari.com
Contact: Kristen Foye Please contact via email. clinical@dantari.com

Locations
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United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
UCLA - Parkside Cancer Center Recruiting
Santa Monica, California, United States, 90404
United States, Florida
H Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Saint Luke's Cancer Institute Recruiting
Jackson, Missouri, United States, 64111
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
United States, Pennsylvania
Magee Women's Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Sarah Cannon Research Institute/Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Dantari, Inc.
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Responsible Party: Dantari, Inc.
ClinicalTrials.gov Identifier: NCT05261269    
Other Study ID Numbers: DAN-22220205
First Posted: March 2, 2022    Key Record Dates
Last Update Posted: October 19, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents