Clinical trial NCT02076451: Open-label Study of DS-8273a to Assess Its Safety and Tolerability, and Assess Its Pharmacokinetic and Pharmacodynamic Properties in Subjects With Advanced Solid Tumors or Lymphomas
Official title: PHASE 1, OPEN-LABEL STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF DS-8273A IN SUBJECTS WITH ADVANCED SOLID TUMORS OR LYMPHOMAS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lymphoma
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2014-03-03
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This will be a Phase 1, open-label study of DS-8273a to assess its safety and tolerability, identify the Maximum Tolerated Dose and/or Maximum Administered Dose, and assess its properties in subjects with advanced solid tumors or lymphomas.

Up to 5 US sites are planned for participation in Part 1 (Dose Escalation) and Part 2 (Dose Expansion) in subjects with solid tumors or lymphomas.


Eligibility criteria: Inclusion Criteria:

* Has a histologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment, and for whom no standard treatment is available.
* Man or woman \>= 18 years old.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Has adequate bone marrow function, defined as: Platelet count \>= 100 X 10\*9/L Hemoglobin level \>= 9.0 g/dL Absolute neutrophil count \>= 1.5 x 10\*9/L
* Has adequate renal function, defined as: Creatinine clearance \>= 60 mL/minute, as calculated using the modified Cockroft Gault equation, (\[{140 - age in years} × {actual weight in kg}\] divided by \[{72 × serum creatinine in mg/dL} multiplied by 0.85 if female\]), OR creatinine \<= 1.5 X upper limit of normal (ULN)
* Has adequate hepatic function, defined as: AST/ALT \<= 3 X ULN (if liver metastases are present, \<= 5 X ULN) Bilirubin \<= 1.5 X ULN
* Has adequate blood clotting function, defined as: International normalized ratio and activated partial thromboplastin time \<= 1.5 X ULN
* Subject should be able to provide written informed consent and comply with protocol visits and procedures.
* Subject (male and female) of childbearing/ reproductive potential must agree to use double barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug.
* Subject must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an Institutional Review Board-approved Informed Consent Form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study specific procedures or tests.
* Is willing to provide pre-existing diagnostic or resected tumor samples, such as paraffin-embedded sections. Providing a fresh tumor biopsy sample is optional.
* Following treatment-free period prior to enrollment to the study: i)Surgery: 4 weeks for major surgery (e.g., laparotomy and thoracotomy); 2 weeks for less extensive surgery (e.g., colostomy) ii)Radiation: 4 weeks (2 weeks for palliative irradiation to bone metastases \[except for pelvic irradiation\], and brain metastasis) iii) Chemotherapy (including systemic treatment with anticancer therapy and retinoid therapy): 3 weeks (6 weeks for nitrosourea antineoplastic agent and mitomycin C) iv) Antibody-based therapy: 4 weeks v) Small molecule targeted agents: If myelosuppression is not expected, 2 weeks or 5 half-lives, whichever is longer; otherwise, 3 weeks vi) Hormonal treatment: 3 weeks. Previous and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted if such therapy has not been changed within 8 weeks before study drug treatment. vii) Pleurodesis: 2 weeks

Exclusion Criteria:

* Has a history of primary central nervous system malignancy.
* Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection.
* Has received an allogeneic bone marrow or allogeneic stem cell transplant.
* Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor.
* Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (2 weeks for stereotactic radiotherapy).
* Has unresolved toxicities from prior anti-cancer therapies, defined as toxicities (chemotherapy, hormonal treatment, radiation, and/or surgery) not yet resolved to NCI-CTCAE, v4, Grade \<= 1 or baseline; other than alopecia, skin toxicity (Grade 1), according to NCI-CTCAE, v4. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator and Sponsor (e.g., Grade 2 chemotherapy-induced peripheral neuropathy).
* Had an autologous transplant within 3 months of starting study drug treatment.
* Participated in a therapeutic clinical study within 3 weeks (2 weeks or 5 half-lives, whichever is longer, for small-molecule targeted agents) before study drug treatment, or current participation in other therapeutic investigational procedures.
* Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is \> 450 ms for males and \> 470 ms for females based on triplicate electrocardiogram (ECG).
* Pregnant or breastfeeding.
* Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
* Prior treatment with a human DR5 agonist.
* Life expectancy \< 3 months in the opinion of the Investigator

Primary outcomes:
measure: number of adverse events
timeFrame: 21 days
measure: maximum tolerated dose
timeFrame: 21 days
Secondary outcomes:
measure: tumor response
timeFrame: 21 days
measure: incidence of human anti-human antibody (HAHA) formation
timeFrame: 21 days
measure: determine the pharmacokinetics of DS-8273a
timeFrame: 21 days
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennesee Oncology
state: Tennessee
Study officials:
References: