Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib (SIGNATURE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01831726
First received: April 11, 2013
Last updated: May 2, 2014
Last verified: May 2014
  Purpose

The purpose of this signal seeking study is to determine whether treatment with dovitinib (TKI258) demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.


Condition Intervention Phase
Tumor Pathway Activations Inhibited by Dovitinib
Drug: Dovitinib (TKI258)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 2 - Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib Including Tumors With Mutations or Translocations of FGFR, PDGFR, VEGF, cKIT, FLT3, CSFR1, Trk and RET

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Clinical benefit associated with dovitinib treatment [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of CR or PR or SD. For hematologic tumors other appropriate hematological response criteria will apply.


Secondary Outcome Measures:
  • Overall Response (OR) of Partial Response (PR) or greater [ Time Frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ] [ Designated as safety issue: No ]
    Overall Response (OR) of Partial Response (PR) or greater based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria will apply and are included in the appendices.

  • Progression-Free Survival (PFS) [ Time Frame: every 8 weeks until death, assessed up to 24 months ] [ Designated as safety issue: No ]
    Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.

  • Overall survival (OS) [ Time Frame: every 8 weeks until death, assessecd up to 36 months ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact

  • Duration of Response (DOR) [ Time Frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ] [ Designated as safety issue: No ]
    The duration of response (PR or greater) applies only to patients whose best response was PR or greater. It is defined as the time from the first documented response to the date first documented disease progression or relapse or death due to any cause

  • Safety and tolerability [ Time Frame: more than 30 days after the last date of study treatment, assessed up to 24 months ] [ Designated as safety issue: Yes ]
    Safety and tolerability will be will be based on the frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g., electrocardiogram, vital signs) will be considered as appropriate


Estimated Enrollment: 70
Study Start Date: August 2013
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dovitinib (TKI258)
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule. A
Drug: Dovitinib (TKI258)
Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.

Detailed Description:

This is a phase II, open label study to determine the efficacy and safety of treatment with dovitinib (TKI258) in patients with a diagnosis of select solid tumors or hematological malignancies that have been pre-identified (prior to study consent) to have mutations, translocations or pathway activations inhibited by dovitinib and whose disease has progressed on or after standard treatment.

Genomic profiling is becoming more accessible to patients and their physicians. As such, more patients have been identified with potentially-actionable mutations, translocations or pathway-activations but do not have access to targeted drug treatment. This is a signal-seeking study to match patients with tumor pathway activations inhibited by dovitinib to the RTK inhibitor dovitinib. Pre-identification of mutations, translocations, or tumor pathway activations inhibited by dovitinib will be performed locally at a CLIA certified laboratory prior to participation on the trial.

Once the patient has been identified, treating physicians who are qualified investigators may contact Novartis to consider enrollment in this study. For the purpose of this study, genomic profiling is not considered part of screening. Informed consent must be signed before any screening activities take place. Once eligibility (screening criteria met) has been confirmed by Novartis, the patient will initiate therapy with dovitinib single-agent. The patient may not receive any additional anti-cancer therapy during treatment with dovitinib.

Patients will continue to receive study treatment until disease progression (assessed by RECIST 1.1 or appropriate hematologic response criteria), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment. All patients who discontinue from study treatment due to disease progression must have their progression clearly documented.

Disease assessment (by RECIST 1.1 or appropriate hematological response assessment criteria) will be performed every 8 weeks (±4 days) after first dose of study drug (Day 1 of every odd cycle), until disease progression or end of treatment, whichever occurs first. The frequency of disease assessment may be reduced to every 12 weeks for patients who have at least 4 post-baseline disease assessments and are clinically stable (except AML patients). Scans will be assessed locally by the investigator. After discontinuation of treatment, patients, regardless of reason for treatment discontinuation, will be followed for safety for 30 days after the last dose.

All patients will be followed for survival status every 3 months for 2 years after the last patient has enrolled in the study,regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has a confirmed diagnosis of a select solid tumor (except primary diagnosis of urothelial tumors, hepatocellular carcinoma (HCC), endometrial carcinoma, metastatic breast cancer (mBC), squamous non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC)) or hematologic malignancies (except primary diagnosis of FLT3 AML or multiple myeloma) and is in need of treatment because of progression or relapse. Additional tumor types may be excluded during the course of the study in the case of early futility or success based upon an interim analysis.
  • Patient's tumor has been evaluated and pre-identified with a relevant pathway activation inhibited by dovitinib at a CLIA certified laboratory
  • Patient must have received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
  • Patient must have progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion Criteria:

  • Patient has received prior treatment with dovitinib (TKI258)
  • Patients with brain metastasis or history of brain metastasis or leptomeningeal carcinomatosis
  • Patient has received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug.
  • Patient is currently receiving prasugrel, clopidogrel, or full dose anticoagulation treatment with therapeutic doses of warfarin. However, treatment with low doses of warfarin (e.g., ≤2 mg/day) or locally accepted low doses of acetylsalicylic acid (up to 100 mg daily) to prevent cardiovascular events or strokes is allowed.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01831726

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Enrollment Call Center 1-855-744-6727

  Show 33 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01831726     History of Changes
Other Study ID Numbers: CTKI258AUS26
Study First Received: April 11, 2013
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
dovitinib
GIST
gastrointestinal stromal tumor
Solid tumor malignancy
hematologic malignancy
mutation
translocations
FGFR
PDGFR
VEGF
cKIT
FLT3
CSR1
Trk
RET
TKI258
signature
AML
acute myelogenous leukemia
Head and Neck cancer
Melanoma
NSCLC
non-small cell lung carcinoma
lung cancer
ovarian cancer
thyroid cancer

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 20, 2014