Combining Selinexor and Talazoparib for Advanced Triple Negative Breast Cancer
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)
This study is testing a combination of two drugs, Selinexor and Talazoparib, to see if they can help people with advanced triple negative breast cancer.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 63 (estimated) |
| Ages | 18 Years to 99 Years |
| Sex | All |
| Sponsor | National University Hospital, Singapore Academic / other |
| Drugs / interventions | lapatinib, chemotherapy, immunotherapy, Radiation |
| Locations | 1 site (Singapore) |
| Trial ID | NCT05035745 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the safety and efficacy of the combination of Selinexor and Talazoparib in patients with advanced refractory solid tumors, specifically focusing on advanced or metastatic triple negative breast cancer (TNBC). The study consists of a phase I dose-finding component followed by a phase II expansion, enrolling a total of 63 patients. The primary goal is to determine the recommended phase II dose (RP2D) and assess the objective response rate in TNBC patients. Additionally, the study will explore pharmacokinetics, pharmacogenetics, and changes in circulating tumor cells and plasma biomarkers during treatment.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with advanced or metastatic triple negative breast cancer who have shown disease progression after at least one line of anti-cancer therapy.
Not a fit: Patients who have previously received treatment with PARP inhibitors or Selinexor may not benefit from this study.
Why it matters
Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced triple negative breast cancer who have limited therapeutic alternatives.
How similar studies have performed: While the combination of these specific agents is novel, previous studies have shown promise in using PARP inhibitors and other targeted therapies in similar patient populations.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Singapore
- National University Hospital — Singapore, Singapore (Recruiting)
Study contacts
- Principal investigator: Soo Chin Lee — National University Hospital, Singapore
- Study coordinator: Soo Chin Lee
- Email: soo_chin_lee@nuhs.edu.sg
- Phone: 6779 5555
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.