Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Selinexor & Talazoparib in Advanced Refractory Solid Tumors; Advanced/Metastatic Triple Negative Breast Cancer (START)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05035745
Recruitment Status : Recruiting
First Posted : September 5, 2021
Last Update Posted : September 5, 2021
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore

Tracking Information
First Submitted Date  ICMJE March 1, 2021
First Posted Date  ICMJE September 5, 2021
Last Update Posted Date September 5, 2021
Actual Study Start Date  ICMJE March 1, 2021
Estimated Primary Completion Date November 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2021)
safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors using NCI CTCAE toxicity grading version 5.0. [ Time Frame: 5 years ]
Patients with advanced/ metastatic triple negative breast cancer, unselected for known platinum sensitivity or resistance, will be enrolled. A pilot of 10 patients will be enrolled. If 0-1 patients achieve an objective response, the combination is deemed to be of no interest for further development. If 2 or more of 10 patients achieve an objective response, another 20 patients will be enrolled to confirm the objective response rate. In the final Safety evaluations will be performed for all patients prior to each cycle of treatment, and include taking a medical history, physical examination, adverse event documentation, full blood count, renal function, liver function tests and electrocardiogram (ECG). Toxicities will be graded using the NCI CTCAE toxicity grading version 5.0.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Selinexor & Talazoparib in Advanced Refractory Solid Tumors; Advanced/Metastatic Triple Negative Breast Cancer (START)
Official Title  ICMJE Phase I Dose Finding Study of Selinexor and Talazoparib in Patients With Advanced Refractory Solid Tumors, Followed by Phase II Expansion Cohort Study in Patients With Advanced/ Metastatic Triple Negative Breast Cancers. (START)
Brief Summary This is a single arm, open-label, phase I dose finding study, followed by a phase II expansion study. Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of 33 patients with refractory solid tumors to determine the RP2D. In the phase II portion, a total of 30 patients with advanced/metastatic TNBC will be enrolled.
Detailed Description

Hypothesis The investigators hypothesize that the combination of Talazoparib and Selinexor will have clinical efficacy in TNBC, independent of BRCA mutation status.

Primary Objectives

  • To determine the safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors.
  • To determine the RP2D of Talazoparib and Selinexor combination therapy in patients with advanced/ metastatic solid tumors.

Secondary Objectives

• To determine the objective response rate to combination Talazoparib and Selinexor in advanced/ metastatic TNBCs.

Exploratory Objectives

  • To assess the effect of the combination on pharmacokinetics of Talazoparib and Selinexor
  • To explore the impact of pharmacogenetics on toxicity and efficacy of combination Talazoparib and Selinexor.
  • To assess changes in circulating tumor cells and plasma biomarkers during treatment.
  • To assess pharmacodynamic changes and predictive biomarkers in tumor tissue during treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

Phase I Patients will be treated with Talazoparib daily and Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days) in a modified 3+3 dose escalation/ de-escalation design

Phase II Patients with advanced/ metastatic triple negative breast cancer, unselected for known platinum sensitivity or resistance, will be enrolled. A pilot of 10 patients will be enrolled. If 0-1 patients achieve an objective response, the combination is deemed to be of no interest for further development. If 2 or more of 10 patients achieve an objective response, another 20 patients will be enrolled to confirm the objective response rate. In the final objective response analysis, TNBC patients will be stratified into platinum-naïve/platinum sensitive versus platinum-resistant to determine if prior platinum sensitivity impacts objective response rates to the combination of Talazoparib and Selinexor.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Refractory Solid Tumors
  • Advanced Triple Negative Breast Cancers
  • Metastatic Triple Negative Breast Cancers
Intervention  ICMJE
  • Drug: Talazoparib
    Patients will be treated with Talazoparib daily on a 4 weekly cycle (28 days)
  • Drug: Selinexor
    Patients will be treated with Selinexor once per week (3 out of 4 weeks), on a 4 weekly cycle (28 days)
Study Arms  ICMJE Experimental: Patients with refractory solid tumors
Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of patients with refractory solid tumors to determine the RP2D.
Interventions:
  • Drug: Talazoparib
  • Drug: Selinexor
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 31, 2021)
63
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2025
Estimated Primary Completion Date November 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. All patients must sign an informed consent in accordance with local institutional guidelines.
  2. All patient must not have received prior PARPi including talazoparib
  3. All patients must not have prior therapy with selinexor.
  4. Age ≥ 18
  5. Estimated life expectancy of at least 12 weeks.
  6. Has recovered from acute toxicities from prior anti-cancer therapies to grade 2 or lower.
  7. a) Dose escalation phase: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have radiological evidence of progressive disease on study entry that is deemed unlikely to benefit from further conventional therapy, or for which no standard therapy is available.

    b) Dose expansion phase: Patients with previously treated, advanced or metastatic histologically or cytologically confirmed triple negative breast cancers. Patients must have evidence of progressive disease on study entry after at least one line of anti-cancer therapy. Patients will be stratified into platinum-naïve (not having been treated with platinums-containing chemotherapy in the neoadjuvant, adjuvant or palliative setting), platinum sensitive (defined as having prior objective response or sustained disease control lasting ≥6 months to platinum-containing chemotherapy in the metastatic setting, or relapsed ≥6 months after completing neoadjuvant or adjuvant platinums-containing chemotherapy), and platinum resistant (defined as having progressive disease as the best response or disease control <6 months to platinum-containing chemotherapy in the metastatic setting, or relapsed <6 months after completing neoadjuvant or adjuvant platinums-containing chemotherapy).

    There is no upper limit on the number of prior treatments provided all inclusion/exclusion criteria are met. Hormone ablation therapy is considered an anti-cancer regimen. Radiation and surgery are not considered anti-cancer regimens.

  8. Measurable disease by RECIST 1.1 criteria.
  9. Eastern cooperative Oncology Group (ECOG) Performance Status of 0-1
  10. Adequate bone marrow function and organ function within 2 weeks of study treatment

    1. Adequate hematologic function defined as:

      • Absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 109/L
      • Platelets ≥ 125 x 109/L during dose escalation phase; platelets ≥ 100 x 109/L during dose expansion phase
      • Hemoglobin ≥ 9 x 109/L
    2. Hepatic function:

      • Bilirubin ≤ 1.5 times the upper limit of normal (ULN)
      • ALT or AST ≤ 2.5 times ULN (or ≤ 5 times ULN with liver metastases)
    3. Adequate renal function:

      • Calculated creatinine clearance of ≥ 60 mL/min, calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg)/(72 x creatinine mg/dL); multiply by 0.85 if female.
  11. Able to swallow tablets/ pills.
  12. Able to comply with study-related procedures.
  13. Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for 7 months following the last dose of study treatment

Exclusion Criteria:

  1. Treatment within the last 30 days with any investigational drug.
  2. Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
  3. Major surgery within 28 days of study drug administration
  4. Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
  5. Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
  6. Pregnancy
  7. Breast feeding
  8. Poorly controlled diabetes mellitus
  9. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment (for phase II only).
  10. Symptomatic brain metastasis.
  11. History of significant neurological or mental disorder, including seizures or dementia.
  12. Unable to comply with study procedures
  13. Current or anticipated use of strong P-gp inhibitors: amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, valspodar, verapamil
  14. Current or anticipated use of strong BCRP inhibitors: curcumin, cyclosporine A, eltrombopag, elacridar, fumitremorgin C, novobiocin, sulfasalazine
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Soo Chin Lee 6779 5555 soo_chin_lee@nuhs.edu.sg
Listed Location Countries  ICMJE Singapore
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05035745
Other Study ID Numbers  ICMJE MC01/05/20; IST-325 (KPT)
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party National University Hospital, Singapore
Study Sponsor  ICMJE National University Hospital, Singapore
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Soo Chin Lee National University Hospital, Singapore
PRS Account National University Hospital, Singapore
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP