Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib (SIGNATURE)
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.
Tumor Pathway Activations Inhibited by Dovitinib
Drug: Dovitinib (TKI258)
|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|
- 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 ≥ 16 weeks. For hematologic tumors other appropriate hematological response criteria will apply.
- 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
|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)|
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.
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 amplifications 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 amplifications 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 amplifications 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 investigator per 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 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)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01831726
|Contact: Novartis Pharmaceuticals||1-888-669-6682|
|Contact: Enrollment Call Center||1-855-744-6727|
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|