Development of a Tumor Molecular Analyses Program and Its Use to Support Treatment Decisions

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01457196
• Collaborator: (none)
• Enrollment: 2,798
• Location: 1
• Arm: 1
• Duration (Months): 81.1
• Patients Per Site Per Month: 34.5

Study Details

Study Description

Brief Summary

The primary objective of this specimen correlative study is two-fold: to provide a mechanism for the association of known molecular alterations with clinical outcomes, and to provide rapid genetic profiling of alterations with known clinical utility using tumor and germline specimens to support treatment decisions.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm	Diagnostic Test: Tumor Genetic Sequencing	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 2798 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Development of a Tumor Molecular Analyses Program and Its Use to Support Treatment Decisions
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Jun 6, 2018
• Actual Study Completion Date: Jun 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Sequencing Arm	Diagnostic Test: Tumor Genetic Sequencing; This study will look at genetic material from a sample of the subjects tumor, look at certain changes in the genetic material, and see if these changes are related to the subjects cancer.

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With a Reportable Genetic Variant [1 year]

   To estimate the proportion of patients enrolled on the study who have undergone successful sequencing and have a reportable genetic variant identified

2. Progression Free Survival [2 Year]

   Estimate Progression Free Survival (PFS) at 2 years in cancer patients with active disease with a reportable genetic variant and those without a reportable genetic variant

Other Outcome Measures

1. Collect and Describe Clinical Data [1 Year]

   To collect and describe clinical data including treatment outcomes after availability of results in patients

2. Progression Free Survival [1 Year]

   To compare progression free survival ratios between cancer patients with active disease with reportable genetic variant who were treated based on variant and those who were not treated based on a variant

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Current or prospective cancer patients; current cancer patients must have histologically or cytologically confirmed diagnosis of cancer

2. Tumor tissue available and suitable for molecular analyses from at least one of the following sources:

• Tissue previously stored in UNC's Tissue Procurement Facility (TPF)

• Tissue previous stored at an institution other than UNC-CH, provided investigators can determine that the tumors were sampled and stored under appropriate conditions for inclusion in the study

• Patient undergoing tissue collection as per clinical standard of care and willing to allow specimens from surplus tissue to be diverted for research purposes

• Patient undergoing tissue collection as per clinical standard of care and willing to have additional specimens taken for research

• Patient willing to undergo biopsy for purpose of research only

1. The following inclusion criteria apply only to patients undergoing biopsy for research purposes only under this protocol:

• ≥18 years of age

• Treatment options offer no expectation of cure, e.g., advanced solid tumor patients with metastatic disease. NOTE: This restriction applies to biopsy of vital organs only, e.g., lung, liver, etc.

• Appropriate candidate for research biopsy based on institutional standards for target biopsy site

Exclusion Criteria:

1. Any condition that would make participation in the protocol unreasonably hazardous for the patient in the opinion of the treating physician

2. Dementia, altered mental status, or any psychiatric condition or co-morbid condition that would prohibit the understanding or rendering of informed consent.

3. The following exclusion criteria apply only to enrolled patients undergoing biopsy for research purposes only:

4. History of serious or life-threatening allergic reaction to local anesthetics (i.e. lidocaine, xylocaine) or any medications used for conscious sedation (if applicable).

5. Requires general anesthesia for collection of biopsy

6. Pregnant or lactating women

7. Active cardiac disease

8. Patients receiving bevacizumab less than 6 weeks prior to enrollment into this study should not undergo research core biopsies because of the concern for potential increased bleeding risk and delayed healing. (NOTE: Patients receiving bevacizumab who are undergoing a research biopsy of accessible organs (e.g. breast, lymph node, skin etc.) must be two weeks from the last dose of the angiogenesis inhibitor).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center

Investigators

• Principal Investigator: H. Shelton Earp, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 25, 2019

More Information

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01457196
• Other Study ID Numbers: LCCC1108
• First Posted: Oct 21, 2011
• Last Update Posted: Dec 30, 2019
• Last Verified: Dec 1, 2019

• Keywords provided by UNC Lineberger Comprehensive Cancer Center: Cancer Genetics

Study Results

Participant Flow

Pre-assignment Detail	Of the 2798 participants screened for eligibility, 2074 were deemed eligible, 459 failed processing/sequencing, 226 had a sample collection failure, 19 were pediatric patients who were excluded from the final cohort, and 20 consents were withdrawn.

Arm/Group Title	Sequencing Arm
Arm/Group Description	All eligible subjects who had Tumor Genetic Sequencing performed. This sequencing looked at genetic material from a sample of the subjects tumor and certain changes in the genetic material, to see if these changes are related to the subjects cancer.
Period Title: Overall Study
STARTED	2074
COMPLETED	2074
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Sequencing Arm
Arm/Group Description	All eligible subjects who had Tumor Genetic Sequencing performed. This sequencing looked at genetic material from a sample of the subjects tumor and certain changes in the genetic material, to see if these changes are related to the subjects cancer.
Overall Participants	2074
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1482 71.5%
>=65 years	592 28.5%
Sex: Female, Male (Count of Participants)
Female	1352 65.2%
Male	722 34.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	67 3.2%
Not Hispanic or Latino	1972 95.1%
Unknown or Not Reported	35 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	13 0.6%
Asian	31 1.5%
Native Hawaiian or Other Pacific Islander	2 0.1%
Black or African American	327 15.8%
White	1573 75.8%
More than one race	3 0.1%
Unknown or Not Reported	125 6%
Region of Enrollment (participants) [Number]
United States	2074 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With a Reportable Genetic Variant
Description	To estimate the proportion of patients enrolled on the study who have undergone successful sequencing and have a reportable genetic variant identified
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sequencing Arm
Arm/Group Description	Tumor Genetic Sequencing: This study will look at genetic material from a sample of the subjects tumor, look at certain changes in the genetic material, and see if these changes are related to the subjects cancer.
Measure Participants	2074
Number (95% Confidence Interval) [proportion of participants]	0.61 0%

2. Primary Outcome

Title	Progression Free Survival
Description	Estimate Progression Free Survival (PFS) at 2 years in cancer patients with active disease with a reportable genetic variant and those without a reportable genetic variant
Time Frame	2 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reported	Not Reported
Arm/Group Description	Subjects with next-generation sequencing who had somatic variants identified by the University of North Carolina (UNC )Molecular Tumor Board as actionable that were unknown at the time of testing reported to their treating physicians.	Subjects with next-generation sequencing who had no somatic variants identified by the UNC Molecular Tumor Board as actionable that were unknown at the time of testing reported to their treating physicians.
Measure Participants	1267	807
Number (95% Confidence Interval) [percentage of participants]	31 1.5%	62 NaN

3. Other Pre-specified Outcome

Title	Collect and Describe Clinical Data
Description	To collect and describe clinical data including treatment outcomes after availability of results in patients
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Progression Free Survival
Description	To compare progression free survival ratios between cancer patients with active disease with reportable genetic variant who were treated based on variant and those who were not treated based on a variant
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	One year
Arm/Group Title	Sequencing Arm
Arm/Group Description	All eligible subjects who had Tumor Genetic Sequencing performed. This sequencing looked at genetic material from a sample of the subjects tumor and certain changes in the genetic material, to see if these changes are related to the subjects cancer.
All Cause Mortality
	Sequencing Arm
	Affected / at Risk (%)	# Events
Total	723/2074 (34.9%)
Serious Adverse Events
	Sequencing Arm
	Affected / at Risk (%)	# Events
Total	0/2074 (0%)
Other (Not Including Serious) Adverse Events
	Sequencing Arm
	Affected / at Risk (%)	# Events
Total	0/2074 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.