Rational Therapeutics Based on Matched Tumor and Normal Tissue

A Study to Select Rational Therapeutics Based on the Analysis of Matched Tumor and Normal Biopsies in Subjects With Advanced Malignancies

The goal of this laboratory research study is to learn if using molecular information (matched therapy) or not using molecular information and having the study doctor choose the therapy based on your past experience are more effective ways to choose the best cancer treatment for you.

This is an investigational study.

Up to 200 participants will take part in this study. Up to 50 will be enrolled at MD Anderson.

Study Overview

• Status: Completed
• Conditions: Advanced Cancers
• Intervention / Treatment: Other: Treatment Based on Genetic Mutation; Other: Treatment Based on No Genetic Mutation

Detailed Description

If you agree to take part in this study, your tumor tissue and blood samples will be tested for molecular profiling. Molecular profiling is the classification of tissue based on the expression of certain genes within a tumor compared to normal tissue. This may be used to predict how the tumor responds to therapy. Your doctor may use the results of the molecular profiling to help decide which treatment might be the most beneficial for the disease.

Study Procedures:

Blood (about 2 teaspoons) will be drawn and you will have a tumor biopsy and a biopsy of normal tissue when you enroll in this study. Blood (about 2 teaspoons) will be drawn again about 2-3 weeks after you begin treatment. The type of biopsy you have will depend on the type of disease you have. The risks of this procedure will be discussed in more detail with you.

If there is not enough tissue with which the study doctor can perform the study tests (described below), you may need to have a second biopsy. The study staff will discuss this with you if it is needed.

Treatment Arms:

A series of tests to find which gene mutations you have, if any, will be performed. Depending on the results of your molecular testing, you may be enrolled on 1 of 2 arms.

If your molecular profile shows that you have a gene mutation that may benefit from study drugs that are believed to target your gene mutation, you will be enrolled in Arm A and will receive these targeted drugs.

If your molecular profile shows that you do not have a gene mutation, you will be enrolled in Arm B. In Arm B, the doctor will choose a therapy based on other studies rather than gene mutation.

Length of Study:

This study will last about 2 years. Your participation on this study will be complete after the last blood draw and tumor biopsy is collected.

• Study Type: Observational
• Enrollment (Actual): 3

Contacts and Locations

Study Locations

• France
  • Villejuif, France, 94805
    • Cancer Institute Gustave Roussy
• Israel
  • Ramat Gan, Israel
    • Chaim Sheba Medical Center at Tel Hasomer
• Spain
  • Barcelona, Spain, 08035
    • Vall D'Hebron University Hospital
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

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

Cancer patients from University of Texas MD Anderson Cancer Center in Houston, Texas, Cancer Institute Gustave Roussy in Villejuif, France, Vall D'Hebron University Hospital in Barcelona, Spain, and Chaim Sheba Medical Center at Tel Hasomer in Ramat Gan, Israel

Description

Inclusion Criteria:

1. Informed consent
2. Any histologic type of metastatic cancer, (except for lung and brain at US sites), in which histologic normal counterpart can be obtained. See list of cancer types included in the trial in Appendix 1.
3. Progression by RECIST (Response Evaluation Criteria In Solid Tumors) or other criteria on at least one prior regimen for advanced disease
4. Ability to undergo a biopsy or surgical procedure to obtain fresh tumor biopsy paired with its normal counterpart
5. Age from 18 years
6. Life expectancy of at least 3 months
7. ECOG Performance status of 0 to 1
8. Measurable or evaluable disease according to RECIST 1.1 criteria
9. For US sites only: advanced cancer patients that have exhausted all effective therapy for their disease and have progressed after previous line of therapy (documented disease progression under last treatment received) and conventional methods of assigning new therapy would not be expected to increase survival by more than 3 months.

Exclusion Criteria:

1. For US sites only: Any patient that might require a lung or brain biopsy are excluded

2. Alteration of organ function or hematopoietic function as defined by the following criteria:

   1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) >2.5 x upper limit of normal (ULN), except for patients with liver metastases, for which AST and ALT > 5.0 ULN is the exclusion criteria.
   2. Bilirubin > 2.0 ULN to allow for Gilberts
   3. Polynuclear neutrophil < 1.5 x 109/L
   4. Platelets < 100 x 10 9/L
   5. Hemoglobin < 90 g/L
   6. Creatinine > 1.5 ULN

   i. Calcemia > 1.5 ULN g. Phosphatemia > 1.5 ULN

3. Coagulation abnormality prohibiting a biopsy
4. Symptomatic or progressive brain metastases detected by radio imaging, or meningeal
5. Patient who received a personalized therapeutic treatment based on molecular anomaly during the treatment period immediately prior to the WINTHER directed treatment (defining the PFS1). Hormonal therapy may be continued during WINTHER suggested therapy. The exclusion of prior matched targeted therapy includes but is not limited to all targeted therapeutics that are EMA approved and genomically matched to patients. If there are questions about whether or not a prior therapy is a matched targeted treatment it will be agreed on by discussion between PIs who are also Clinical Management Committee members; the resolution should take place prior to starting Winther directed treatment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm A - Treatment Based on Genetic Mutation; Participant's molecular profile shows that they have a gene mutation that may benefit from study drugs that are believed to target their gene mutation. Participant assigned to Arm A and will receive these targeted drugs.	Other: Treatment Based on Genetic Mutation; Participant's molecular profile shows that they have a gene mutation that may benefit from study drugs that are believed to target their gene mutation. Participant assigned to Arm A and will receive these targeted drugs.
Arm B - Treatment Based on No Genetic Mutation; Participant's molecular profile shows that they do not have a gene mutation. Participant assigned to Arm B in which doctor chooses a therapy based on other studies rather than gene mutation.	Other: Treatment Based on No Genetic Mutation; Participant's molecular profile shows that they do not have a gene mutation. Participant assigned to Arm B in which doctor chooses a therapy based on other studies rather than gene mutation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression-free survival (PFS) of the last therapeutic line (PFS1) before entering into study, with the PFS2 under study treatment. A clinical meaningful improvement is defined as demonstrating a PFS ratio (PFS2/PFS1) of being 1.5 or better.	2 - 3 weeks after treatment begins

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: European Commission
• Investigators: Principal Investigator: Apostolia M. Tsimberidou, MD, PhD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2014
• Primary Completion (Actual): January 11, 2022
• Study Completion (Actual): January 11, 2022

Study Registration Dates

• First Submitted: October 20, 2014
• First Submitted That Met QC Criteria: October 21, 2014
• First Posted (Estimate): October 23, 2014

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 11, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Advanced cancers; Molecular profiling; Genetic Mutation; Biologic Markers; Molecular testing; Molecular information
• Other Study ID Numbers: PA12-0381

Drug and device information, study documents

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