Advanced Refractory Solid Tumors With TP53 Mutations Register Study

Prospective and Retrospective Register Study of PARP-Inhibitors Combined With VEGFR-Inhibitors for Treatment of Advanced Refractory Solid Tumors Patients With TP53 Mutations

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 .

Study Overview

• Status: Unknown
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Other: Data Collection

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.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300211
      • Tianjin Medical Unversity Second Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Advanced refractory tumor solid tumors patients; Patients with advanced refractory solid tumors carrying TP53 mutations and receive PARP-inhibitors in combination with the VEGFR-inhibitors therapy	Other: Data Collection; Colleciton of data from medical records only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR(Objective Response Rate)	ORR is the percentage of participants with best overall response of complete response (CR), partial response (PR). Response categories: CR, PR, SD (stable disease), PD (progressive disease) Criteria on which physicians determined therapy response also will be captured by using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 to evaluate.	Up to three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS (Progression Free Survival), calculated from various time points	Progression-free survival (PFS) is defined as progression free survival of all the evaluable participants who receive targeted drug therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1).	Up to two years
OS (Overall Survival), calculated from various time points	OS is defined as time from initiation to death of any cause.	Duration of time from the start of treatment to date of death, assessed up to two years
ADR (Adverse Drug Reaction)	Adverse events determined according to CTCAE (version 4.03).	30 days after last dose

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): January 31, 2020

Study Registration Dates

• First Submitted: April 22, 2019
• First Submitted That Met QC Criteria: April 24, 2019
• First Posted (Actual): April 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 20, 2019
• Last Update Submitted That Met QC Criteria: August 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Solid tumor; TP53; VEGFR; PARP
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: PV-TP53

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No