A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas

NCT01588678 | Completed Phase 1

• 1 other identifier: DS3078-A-U101
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

DS-3078a will be evaluated as a single agent in subjects with advanced solid tumor malignancies or lymphomas refractory to standard treatment or for which no standard treatment is available.

Conditions

Advanced Solid Tumor; Lymphoma

Keywords

endometrial; prostate; breast; gastric; cervical; ovarian; neuroendocrine cancers; soft-tissue sarcoma; squamous cell NSCLC; renal cell carcinoma; non-Hodgkin lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  To determine the maximum tolerated dose (MTD) and tentative recommended Phase 2 dose (RP2D) of DS 3078a

  3 years

Secondary Outcomes (8)

• determine the Cmax profile of DS 3078a

  3 years

• effect on glucose metabolism

  3 years

• assess pharmacodynamic effects tumor glucose uptake

  3 years

• assess tumor response

  3 years

• assess pharmacodynamic effects v-akt murine thymoma viral oncogene

  3 years

Study Arms (1)

DS-3078a

EXPERIMENTAL

Part 1 - Dose escalation of DS-3078a to determine the maximum tolerated dose (MTD) will be guided by the modified continuous reassessment method (mCRM) using a Bayesian logistic regression model (BLRM) following escalation with overdose control (EWOC) principle. Before starting mCRM, initial dose escalation will proceed following an accelerated titration in which single subjects will be enrolled into sequential dose levels with a dose increment of up to 100% from the previous dose. Upon completion of Part 1 with established MTD and tentative recommended phase 2 dose (RP2D), the Dose Expansion (Part 2) will begin with the intention of further assessing the safety and tolerability of DS-3078a, confirming the RP2D, determining the Pharmacodynamic response in tumor samples, and evaluating preliminary efficacy of DS-3078a in subjects.

Drug: DS-3078a

Interventions

DS-3078a DRUG

DS-3078a will be administered as oral capsules once daily and will be supplied in 5, 20, 50, and 150 mg capsules.

DS-3078a

Eligibility Criteria

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

You may qualify if:

• A pathologically or cytologically documented advanced solid tumor or lymphoma that has relapsed from or is refractory to standard treatment or for which no standard treatment is available.
• Men or women \>=18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status =\<1
• Have adequate bone marrow function, defined as:
• Platelet count \>=100 x 10\^9/L for solid tumors and \>=75 x 10\^9/L for lymphomas,
• Hemoglobin level \>=9.0 g/dL, and ANC \>=1.5 x 10\^9/L for solid tumors and \>=1.0 x 10\^9/L for lymphomas.
• Have adequate renal function, defined as:
• Creatinine clearance \>=60 mL/min, or creatinine =\<1.5 x ULN.
• Have adequate hepatic function, defined as:
• AST/ALT levels =\<3 x ULN (=\<5 x ULN if liver metastases are present) and
• Bilirubin =\<1.5 x ULN.
• Have adequate blood clotting function, defined as prothrombin time and activated partial thromboplastin time =\<1.5 x ULN.
• Subjects 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/Ethics Committee-approved informed consent form (including Health Insurance Portability and Accountability Act authorization, if applicable) before performance of any study specific procedures or tests.
• For Part 2
• A pathologically or cytologically documented advanced solid tumor or non-Hodgkin lymphoma, with measurable disease based on RECIST 1.1 or revised IWG criteria, that is refractory to standard treatment. The solid tumor types that will be included in the study are of the following kinds in which the mTOR signaling is frequently activated: endometrial, prostate, breast, gastric, cervical,ovarian, or neuroendocrine cancers, soft-tissue sarcoma, squamous cell NSCLC,renal cell carcinoma or other tumor types approved by the Sponsor.

You may not qualify if:

• History of primary central nervous system malignancies
• Gastrointestinal diseases that could affect the absorption of DS-3078a in the opinion of the Investigator
• Subjects with a fasting glucose \>126 mg/dL (\>7 mmol/L)
• History of diabetes mellitus (type 1 or 2) or glycosylated hemoglobin \>7.0% at screening
• Positive test for hepatitis B surface antigen or hepatitis C antibody
• Recipient of live vaccine within 1 month of or during study drug treatment
• Use of chronic systemic corticosteroids (use of nasal or inhaled steroids is permitted)
• Subjects requiring daily supplemental oxygen
• Recipient of an allogenic stem cell or bone marrow transplant
• Presence of 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.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v4 grade =\<1 or baseline.
• Systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy 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 targeted agents within 2 weeks or 5 half-lives before study drug treatment, whichever is longer.
• Therapeutic radiation 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 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 investigational procedures

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (1)

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Lymphoma; Sarcoma; Carcinoma, Renal Cell; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

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

Study Record Dates

• First Submitted: April 26, 2012
• First Posted: May 1, 2012
• Study Start: April 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: February 12, 2019

Record last verified: 2015-04

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 (1)