Clinical trial NCT03927599: Advanced Refractory Solid Tumors With TP53 Mutations Register Study
Official title: Prospective and Retrospective Register Study of PARP-Inhibitors Combined With VEGFR-Inhibitors for Treatment of Advanced Refractory Solid Tumors Patients With TP53 Mutations
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Solid Tumor, Adult
Keywords: TP53
PARP
VEGFR
Solid tumor
Lead sponsor: Tianjin Medical University Second Hospital
Sponsor class: OTHER
First posted: 2019-04-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The objective is to describe in a real-world population.First of all, this study will be carried out as a retrospective, observational review of patients who clinically diagnosed as advanced refractory solid tumors received PARP-inhibitors combined with VEGFR-inhibitors drug therapy, from January 01, 2016 to August 01, 2018. The TP53 gene status must confirm by NGS (Next Generation Sequencing). Then, the investigators prospective observation effectiveness and safety of PARP-inhibitors combined with VEGFR-inhibitors therapy for patients who clinically diagnosed as advanced refractory solid tumors according to the inclusion and exclusion criteria. Those patients should have a NGS report to show the TP53 gene status.

Brief summary: The efficacy and safety of the PARP inhibitor in combination with the VEGFR inhibitor will be investigated in advanced refractory solid tumors patients with TP53 mutation .

Detailed description: TP53 is a well-known tumor suppressor gene. Multiple studies have demonstrated that TP53 mutations are poor prognostic factor in advanced solid tumor, the TP53 gene is frequently inactivated by mutation in a majority of human tumors. However, no effective TP53 -based therapy has been successfully translated into clinical cancer treatment. So, investigators intend to review and evaluate the efficacy and safety of the PARP inhibitor in combination with the VEGFR inhibitor for TP53 mutation in advanced refractory solid tumors patients from a real-world population.

Eligibility criteria: Inclusion Criteria:

1. Is equal to or greater than 18 years of age.
2. Histologic or cytologic confirmation of advanced refractory solid tumors with no standard treatment options, including some patients with advanced disease in reduced general condition (Eastern Cooperative Oncology Group (ECOG) 3 and 4).
3. Patients with measurable or evaluable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
4. Patients must be able to provide blood samples or tissue samples for NGS (Next Generation Sequencing) testing for understanding the TP53 gene status. The amount of blood and tissue samples should be able to meet the requirements of DNA extraction and quality control.
5. Adequate baseline organ system function.
6. Patients could receive treatment program from MTB (Molecular Tumor Board).
7. No prior treatment with PARP combined with VEGFR inhibitions.
8. Ability to understand and the willingness to provide a written informed consent document.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.
2. Prior anti-cancer therapy or radiation therapy within 2 weeks prior to enrolment. Palliative radiotherapy to metastatic lesion(s) permitted providing that it has been completed at least 2 days prior to enrolment and no significant toxicity are expected.
3. Clinically significant (active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study enrollment; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication.
4. Active infection requiring systemic therapy.
5. Patients unable to swallow orally administered medication.
6. Prior treatment with PARP or VEGFR inhibitions.
7. According to the investigator'judgment, there are serious, uncontrollable risks to patients'safety, or associated diseases (such as severe diabetes, thyroid disease, infection, spinal cord compression, superior vena cava syndrome, neurological or psychiatric disorders and so on) that affect the patients completion of the study.

Primary outcomes:
measure: ORR(Objective Response Rate)
timeFrame: Up to three months
Secondary outcomes:
measure: PFS (Progression Free Survival), calculated from various time points
timeFrame: Up to two years
measure: OS (Overall Survival), calculated from various time points
timeFrame: Duration of time from the start of treatment to date of death, assessed up to two years
measure: ADR (Adverse Drug Reaction)
timeFrame: 30 days after last dose
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical Unversity Second Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical Unversity Second Hospital
name: Haitao Wang
role: PRINCIPAL_INVESTIGATOR
References: