A Study of DS-2248 in Participants With Advanced Solid Tumors

NCT01288430 | Terminated Phase 1 Results

• 2 other identifiers: DS2248-A-U1012011-002666-21
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 9

Brief Summary

This phase 1 clinical trial is intended to understand the safety and tolerability of a new anticancer drug in subjects with advanced solid tumors. The patients who qualify for the study will receive a once daily dose of the drug taken by mouth and will undergo several tests to measure the drug in the blood and to understand the safety, tolerability and any effect of the drug on the tumor. The antitumor effect of the drug is not known in human.

Conditions

Solid Tumors; Non-small Cell Lung Carcinoma

Keywords

Heat shock protein 90; Advanced solid tumors; Non-small cell lung carcinoma; Epidermal growth factor receptor; Tyrosine kinase inhibitor acquired resistance; Non-small cell lung carcinoma with acquired resistance to erlotinib, gefitinib, afatinib or others.

Outcome Measures

Primary Outcomes (1)

• Summary of Objective Response Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors

  Objective response rate was defined as the sum of complete response (CR) and partial response (PR) rates. CR was defined as a disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

Secondary Outcomes (10)

• Summary of Best Overall Response Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors

  Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

• Summary of Disease Control Rate Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors

  Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

• Duration of Stable Disease Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors

  Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

• Summary of Progression-free Survival Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors

  Baseline up to disease progression, discontinuation of study, or death, up to 2 years 11 months

• Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Infinity Following Oral Administration of DS-2248 in Participants With Advanced Solid Tumors

  Cycle 1, Day 1 predose, 0.5, 1, 2, 3, 4, 6, and 8 h postdose; Cycle 1, Day 2 and Day 15; Cycle 1, Day 8 predose, 1 and 6 h postdose; Cycle 2 and 3, Day 1, 8, and 15

Study Arms (1)

DS-2248

EXPERIMENTAL

Study Part 1: DS-2248 oral capsule(s) of increasing strength in a dose escalation study in subjects with advanced solid tumors, administered once daily in 21-day cycles, with no interruption between cycles if no unacceptable treatment-related toxicity or tumor progression is observed. Study Part 2: DS-2248 oral capsule(s) dose of 4.5 mg/m\^2, in subjects with non-small cell lung cancer who have developed acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors or whose tumors carry an ALK translocation and are resistant to ALK inhibitor therapy, administered once daily in 21 day-cycles, with no interruption between cycles if no unacceptable treatment-related toxicity or tumor progression are observed.

Drug: DS-2248

Interventions

DS-2248 DRUG

Oral capsules, of various strengths (1, 5 , 20 ,or 50 milligrams), once daily during 21-day cycles, until unacceptable treatment-related toxicity or tumor progression are observed.

DS-2248

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A pathologically documented advanced solid malignant tumor refractory to standard treatment or for which no standard treatment is available.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Have adequate bone marrow function, defined as:
• Platelet count ≥100x10\^9/L or more.
• Hemoglobin (Hb) level ≥9.0 g/dL.
• Absolute neutrophil count ≥1.5 x 10\^9/L.
• Have adequate renal function, defined as:
• \- Creatinine clearance ≥60 mL/min, as calculated using the modified Cockcroft-Gault equation AND creatinine ≤1.5 times upper limit of normal(ULN).
• Have adequate hepatic function, defined as:
• Aspartate aminotransferase (AST) levels ≤3 times ULN (if liver metastases are present, ≤5x ULN)
• Alanine aminotransferase (ALT) levels ≤3x ULN (if liver metastases are present, ≤5x ULN
• Bilirubin ≤1.5x ULN
• Have adequate blood clotting function, defined as:
• \- Prothrombin time and activated partial thromboplastin time ≤1.5x ULN
• Participants should be able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or chronic co-morbidity that would interfere with therapy.

You may not qualify if:

• History of second malignancies or primary central nervous system malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years.
• Gastrointestinal diseases that could affect the absorption of DS-2248.
• Subjects with peptic ulcer disease requiring on-going treatment with pH-modifiers
• Subjects with history of inflammatory bowel disease.
• Subjects with retinal or uveal diseases including macular degeneration with central vision loss, retinal detachment, diabetic retinopathy, and uveitis.
• Recipient of a stem cell or bone marrow transplant.
• Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor.
• 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 previous anti-cancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, Grade ≤1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator or Sponsor (e.g., Grade 2 chemotherapy-induced neuropathy).
• Systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy (except megestrol acetate as supportive care) within 3 weeks before study drug treatment; or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment; or treatment with small-molecule Tyrosine Kinase Inhibitors within 7 days for erlotinib and afatinib and 10 days for gefitinib before study drug treatment. 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.
• Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug treatment.
• Participation in a clinical drug study within 3 weeks for small-molecule TKIs before study drug treatment, or current participation in other investigational procedures.
• Concomitant treatment with potent inducers or potent inhibitors of cytochrome P450 3A4 (CYP3A4).
• Concomitant treatment with a medication known to cause renal tubular damage or reduce renal perfusion at the dose administered, including aminoglycosides, amphotericin B, pentamidine, nonsteroidal anti-inflammatory drugs, and zoledronate.
• Corrected QT interval (QTc by Bazett's formula) prolongation at rest, where the mean QTc interval is \>450 msec based on triplicate ECG.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Daiichi Sankyo UK Ltd.: collaborator

Study Sites (9)

Unknown Facility

Duarte, California, United States

Location

Unknown Facility

Loma Linda, California, United States

Location

Unknown Facility

Orange, California, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Detroit, Michigan, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2011
• First Posted: February 2, 2011
• Study Start: March 29, 2011
• Primary Completion: February 13, 2014
• Study Completion: February 13, 2014
• Last Updated: October 5, 2021
• Results First Posted: July 10, 2020

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (9)