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Treatment Resistance Following Anti-cancer Therapies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04436120
Recruitment Status : Terminated (COVID-19 pandemic related enrollment pause)
First Posted : June 17, 2020
Last Update Posted : January 26, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

The TRANSLATE study aims to better understand why tumors become resistant to standard anti-cancer therapies.

New tumor biopsy and blood samples are collected after disease progression on standard-of-care anti-cancer treatment and compared to the initial (archival) tumor biopsy sample taken from the same patient.

Annotated reports of results from clinical Next Generation Sequencing (NGS) gene panel tests of both tumor and blood are sent directly from the testing lab to the study physician for discussion with the patient during the study.

Patients may participate in interventional treatment clinical trials at the same time as participating in the TRANSLATE study.

Primary data will be publicly available after the study to support further research.


Condition or disease Intervention/treatment Phase
Disease Progression Procedure: De novo tumor tissue biopsy Procedure: Research blood draws Not Applicable

Detailed Description:

Background: Development of new cancer treatments requires better understanding of why tumors develop resistance to standard-of-care (SOC) therapies. However, post-progression tumor biopsies are not routinely collected, limiting the tissue available to characterize mechanisms of treatment resistance. The TRANSLATE clinical study is specifically designed to address these critical gaps.

Trial design: TRANSLATE is a global, multicenter, translational study designed to collect and compare archival pre-treatment tumor tissue with paired de novo tumor and blood samples obtained following disease progression on SOC therapies, targeting therapeutically important areas of cancer biology.

Eligible Tumor Type and Most Recent SOC Therapy:

  • Non-small-cell lung and Anti-PD-1/-L1 monotherapy
  • Non-small-cell lung and Anti-PD-1/-L1 + platinum
  • Clear cell renal cell carcinoma and Anti-PD-1/-L1 monotherapy
  • Clear cell renal cell carcinoma and Doublet anti-PD-1/-L1 + anti-CTLA-4
  • Clear cell renal cell carcinoma and Pembrolizumab + axitinib
  • Clear cell renal cell carcinoma and Avelumab + axitinib
  • HR+ HER2- breast and Palbociclib + hormonal therapy
  • germline mutated BRCA breast and Olaparib or talazoparib monotherapy
  • Castration-resistant prostate and Enzalutamide
  • Castration-resistant prostate and Abiraterone + prednisone

Eligibility criteria include adults with locally advanced or metastatic tumors; radiographic evidence of progressive disease during the most recent SOC regimen; sufficient archival tumor tissue; and a post-progression tumor lesion that is safely accessible for a new biopsy.

The results from clinical NGS panel testing may help inform subsequent treatment plan or identification of relevant interventional clinical trials.

Patients are enrolled after disease progression on SOC and before change in treatment and participate in 3 study visits within approximately 3 months.

Next-generation sequencing results from analysis of tumor tissue and blood will be returned to the study physician and patient for review at a subsequent study visit within this timeframe.

The primary endpoint is the change in frequency of gene alterations between pre-treatment and post-progression tumor biopsies. Secondary endpoints address prioritized scientific hypotheses specific to each target area of biology and indication.

Primary data will be publicly available after the study to support further research.

Sponsored by Pfizer Inc.; EudraCT: 2018-003612-45.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: TREATMENT RESISTANCE FOLLOWING ANTI-CANCER THERAPIES (TRANSLATE)
Actual Study Start Date : February 13, 2019
Actual Primary Completion Date : December 14, 2020
Actual Study Completion Date : December 14, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy

Arm Intervention/treatment
Tumor biopsy and blood draw
Tumor biopsy and blood draw
Procedure: De novo tumor tissue biopsy
De novo tissue biopsy performed following disease progression

Procedure: Research blood draws
Blood biospecimens collected following disease progression




Primary Outcome Measures :
  1. Change in the frequency of gene alterations between pre treatment tumor samples and post progression tumor biopsies [ Time Frame: Through study completion, approximately 3 months ]

Secondary Outcome Measures :
  1. Proportion of patients with fully evaluable archival and post progression tumor biopsy (eg, sample sufficient for all intended analyses at all measured time points) [ Time Frame: Through study completion, approximately 3 months ]
  2. Concordance of gene alterations between post progression biopsy tissue and blood NGS results [ Time Frame: Through study completion, approximately 3 months ]
  3. Change in the frequency of alterations in genes encoding HLA, Beta-2 Microglobulin, STAT1, JAK1, JAK2, IFN-gamma and IFN- gamma R between pre treatment archival and post progression samples [ Time Frame: Through study completion, approximately 3 months ]
  4. Frequency of alterations in genes encoding HLA, Beta 2 Microglobulin, STAT1, JAK1, JAK2, IFN-gamma and IFNGR in cfDNA [ Time Frame: Through study completion, approximately 3 months ]
  5. Change in the frequency of RB1 gene alterations between pre treatment archival and post progression samples [ Time Frame: Through study completion, approximately 3 months ]
  6. Frequency of RB1 gene alterations in cfDNA [ Time Frame: Through study completion, approximately 3 months ]
  7. Change in the frequency of AR gene alterations between pre treatment archival and post progression samples [ Time Frame: Through study completion, approximately 3 months ]
  8. Frequency of AR gene alterations in cfDNA [ Time Frame: Through study completion, approximately 3 months ]
  9. Changes in the expression of nuclear hormone receptors or related RNA signatures reflecting nuclear receptor pathway activity between pre treatment archival and post progression samples [ Time Frame: Through study completion, approximately 3 months ]
  10. Change in the frequency of somatic reversion alterations in gBRCA mutant allele between pre treatment archival and post progression samples [ Time Frame: Through study completion, approximately 3 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors treated as follows:
  • Non small cell lung carcinoma (NSCLC) monotherapy: Disease progression (PD) on 1st line monotherapy anti PD-1/ L1.
  • NSCLC combination: PD on 1st line anti PD-1/ L1 plus standard doublet platinum containing regimen; or PD on 1st-line anti-PD-1/-L1 plus standard doublet platinum-containing regimen followed by continuation of single agent anti-PD-1/-L1).
  • Renal cell carcinoma (RCC) with clear cell component: PD on 2nd line monotherapy anti PD-1/ L1; or PD on 1st line combination of doublet anti-PD-1/ L1 with anti-CTLA-4; or PD on 1st-line combination of avelumab with axitinib or pembrolizumab with axitinib.
  • HR+ HER2 adenocarcinoma of the breast: PD on 1st line combination of doublet palbociclib with hormonal therapy.
  • Castrate resistant adenocarcinoma of the prostate: PD on enzalutamide monotherapy.
  • Castrate resistant adenocarcinoma of the prostate: PD on abiraterone in combination with prednisone.
  • germline mutated BRCA (gBRCAm), HER2- breast cancer: PD on a PARP inhibitor monotherapy in patients previously treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.
  • Radiographic evidence of PD, including the target lesion being subjected to biopsy for the study, on the most recent regimen that requires a change in anti-cancer treatment.

Exclusion Criteria:

  • Tumor biopsy taken from a bone or an irradiated target lesion.
  • Discontinuation of current or most recent anti cancer therapy due to toxicity and not progressive disease.
  • Initiation of new anti-cancer therapy after disease progression prior to planned biopsy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04436120


Locations
Show Show 33 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04436120    
Other Study ID Numbers: A9001502
TRANSLATE ( Other Identifier: Alias Study Number )
2018-003612-45 ( EudraCT Number )
First Posted: June 17, 2020    Key Record Dates
Last Update Posted: January 26, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Non Small Cell Lung Cancer
Renal Cell Carcinoma
HR+ HER2- Breast Cancer
Castrate-Resistant Prostate Cancer
Germline mutated BRCA, HER2- Breast Cancer
Additional relevant MeSH terms:
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Disease Progression
Disease Attributes
Pathologic Processes