MyCustom:Prospective Master Protocol Trial on Precision Medicine Treatment for Refractory Solid Tumors

MyCustom:A Framework for Prospective and Master Protocol Trial of Precise Drug Treatment for Refractory Solid Tumors

The MyCustom study is a investigator initiated trial(IIT), prospective real-world clinical research project, a genetic biomarker-driven "basket" (tissue-type agonistic) study. The target population covers a variety of solid advanced malignant tumors, including but not limited to patients with small cell lung, gastric, prostate, bladder cancer, head and neck squamous carcinoma or lacking effective treatment after standard treatment failure.

Study Overview

• Status: Recruiting
• Conditions: Refractory Solid Tumors; Next Generation Sequencing

Detailed Description

The MyCustom study is a investigator initiated trial(IIT), prospective real-world clinical research project, a genetic biomarker-driven "basket" (tissue-type agonistic) study. The target population covers a variety of solid advanced malignant tumors, including but not limited to patients with small cell lung, gastric, prostate, bladder cancer, head and neck squamous carcinoma or lacking effective treatment after standard treatment failure.The overall goal is to develop a more effective research method to test new individualized treatment hypotheses.This study will provide comprehensive theoretical and practical support for individualized custom model in refractory solid tumors.Archival pathology laboratory samples from patients with treatment-refractory advanced solid cancer of any histologic type undergo Next Gene Sequencing(NGS) analysis.Fllowing obtain the raw data of the patient's gene sequencing, the data are analyzed by the auxiliary decision algorithm to obtain the prioritization results of the drugs matched by this patient.The results are subsequently reviewed by the Molecular Tumor Board (MTB), where eligible patients can be treated in treatment substudies.All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including clinical efficacy ,clinical safety and exploratory endpoints such as biomarkers for drug response, change in the tumor microenvironment. For some clinical studies, to meet the primary objective, at least 35% of participants had to achieve a PF2S/PFS1 ≥ 1.3 in a sample population of 25 evaluable patients. sample size was calculated using an exact single-stage design for phase II studies with a one-sided type I error of 5% and a power of 90% under the assumption that PF2S/PFS1≥ 1.3 in ≤10% of patients would be clinically irrelevant, while a success rate ≥ 35% would merit further investigation.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Haitao Wang, Ph.D; Phone Number: +86-022-88326610; Email: peterrock2000@126.com
• Study Contact Backup: Name: Lili Wang, M. Med.; Phone Number: +86-022-88326610; Email: 412526928@qq.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300211
      • Recruiting
      • Tianjin Medical University Second Hospital
      • Contact: Haitao Wang, Ph.D; Phone Number: +86-022-88326791; Email: peterrock2000@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients have an advanced or metastatic solid tumor, multiple cancers(including but not limited to small cell lung cancer, gastric cancer, prostate cancer, bladder cancer, and head and neck squamous cell carcinoma) standard treatment options are no longer available or lack effective treatments.

Description

Inclusion Criteria:

1. Adults(≥18 years of age)with pathologically confirmed advanced or metastatic solid cancer of any histological type, or an earlier diagnosis of cancer with a poor prognosis. Suffificient accessible tissue for molecular profifiling;
2. Patients receiving their last line of standard treatment or who have received and failed all standard anticancer therapy (if available) or are unsuitable for further standard anticancer therapy. Cancers with a poor prognosis or low expected response rate to standard treatment (as judged by the investigator on the basis of available evidence) may be screened with respect to an earlier line of treatment;
3. ECOG performance status of 0-4(Poor performance status caused by tumor diseases(3-4));
4. Willing and potentially able to comply with study requirements,including treatment, timing and nature of required assessments;
5. Signed, written informed consent to participate.

Exclusion Criteria:

1. Suitable for standard therapy;
2. Specific contraindications to exposure to the investigationalproducts;
3. Other comorbid conditions that may compromise assessing key outcomes or, in the judgement of the clinician, limit the ability of the patient to comply with the protocol;
4. Symptoms and uncontrolled central nervous system (CNS) involvement in a patient with a non-central cancer;
5. Pregnancy, lactation or inadequate contraception.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cohort-A: Patients with actionable targets; In the OncoKB(Precision Oncology Knowledge Base) database, the gene alteration has a variant of clinical evidence in this tumor or other tumor types and is considered to be an interventional variant. Cohort-A may include different observation subgroups. For example, substudy-A1: monotherapy/combination therapy for patients with A1-relative. Substudy-Ax: monotherapy/combination therapy for patients with Ax-relative.
Cohort-B: Patients with potential actionable targets; In cohort-B, the gene alteration that MTB combines with clinical practice and literature reports that can match targeted therapy is considered to be potential actionable targets. Cohort-B also includes different observation subgroups and clinical trials may conduct in each subgroup. For example, substudy-B1(TP53 as driver gene), substudy-B2(RAS as driver gene), substudy-B3(MAP2K1 as driver gene), substudy-B4(PTEN Loss as driver gene), substudy-B5(11q13 co-amplification as driver genes), Substudy-B6(concomitant actionable alterations), substudy-B7(other driver genes). MTB-guided therapy was defined as having a clinical benefit if the PFS ratio between the longest PFS on MTB-guided therapy and the PFS on the last therapy before MTB-guided therapy was ≥1.3 (i.e., using patients as their own controls) for each substudy. To meet the primary objective, at least 35% of participants had to achieve a PF2S/PFS1 ≥ 1.3 in a sample population of 25 evaluable patients.
Cohort-C: Patients with non-actionable targets; MTB combined with clinical practice and literature reports can not match the gene alteration of targeted therapy, which is considered as an irreversible gene alteration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS2/PFS1(Progression Free Survival 2/Progression Free Survival 1)	The time to progression-free survival during the substudy (PFS2) exceeds the documented time to disease progression-free survival during the last treatment prior to substudy entry (PFS1) by at least 35% (ie, PFS2/PFS1≥1.3) or, if PFS1 is not evaluable, time to progressive disease exceeds 6 months.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR(Objective Response Rate)	Evaluation of the best objective response rate (ORR) for each treatment according to RECIST 1.1. The best ORR is the best response reached during treatment according to RECIST 1.1 criteria.	3 years
OS(Overall Survival)	Evaluation of overall survival (OS) defined as the time between inclusion and death, whatever the cause is. Alive patients will be censored at their last known contact date.	3 years
Number of treatment related adverse events with grade 3 or greater severity by CTCAE 5.0	Treatment related adverse events with grade 3 or greater severity by CTCAE 5.0.	3 years
Proportion of patients with actionable target	Number of patients with modifiable genomic variants.	3 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital
• Investigators: Principal Investigator: Haitao Wang, Ph.D, Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): December 30, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: September 2, 2023
• First Submitted That Met QC Criteria: September 2, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 2, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Precision medicine; NGS; Molecular Tumor Board(MTB)
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: MyCustom for Solid Tumors

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