SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02154490

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)

This screening and multi-sub-study randomized phase II/III trial will establish a method for genomic screening of similar large cancer populations followed by assigning and accruing simultaneously to a multi-sub-study hybrid ?Master Protocol? (S1400). The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned to compare new targeted cancer therapy, designed to block the growth and spread of cancer, or combinations to standard of care therapy with the ultimate goal of being able to approve new targeted therapies in this setting. In addition, the protocol includes a ?non-match? sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies. This sub-study will compare a non-match therapy to standard of care also with the goal of approval.

NCT02154490 Recurrent Squamous Cell Lung Carcinoma Stage IV Squamous Cell Lung Carcinoma AJCC v7
MeSH: Carcinoma Lung Neoplasms
HPO: Carcinoma Neoplasm of the lung

13 Interventions

Name: Docetaxel

Description: Given IV

Type: Drug

S1400A Arm II (CLOSED TO ACCRUAL 4/2015) S1400B Arm II (CLOSED TO ACCRUAL 12/18/2015) S1400C Arm II (CLOSED TO ACCRUAL 12/18/2015) S1400D Arm II (CLOSED TO ACCRUAL 10/31/2016)

Name: Durvalumab

Description: Given IV

Type: Biological

S1400A Arm I (MEDI4736) (CLOSED TO ACCRUAL 12/2015) S1400A Arm III (MEDI4736) S1400F (durvalumab, tremelimumab)

Name: Erlotinib Hydrochloride

Description: Given PO

Type: Drug

S1400E Arm I (CLOSED TO ACCRUAL 11/2014) S1400E Arm II (CLOSED TO ACCRUAL 11/2014)

Name: FGFR Inhibitor AZD4547

Description: Given PO

Type: Drug

S1400D Arm I (AZD4547) (CLOSED TO ACCRUAL 04/12/2017) S1400D Arm III (AZD4547) (CLOSED TO ACCRUAL 10/31/2016)

Name: Ipilimumab

Description: Given IV

Type: Biological

S1400I Arm I (nivolumab, ipilimumab)

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

S1400A Arm I (MEDI4736) (CLOSED TO ACCRUAL 12/2015) S1400A Arm II (CLOSED TO ACCRUAL 4/2015) S1400A Arm III (MEDI4736) S1400B Arm I (taselisib) (CLOSED TO ACCRUAL 12/12/2016) S1400B Arm II (CLOSED TO ACCRUAL 12/18/2015) S1400B Arm III (taselisib) (CLOSED TO ACCRUAL 12/12/2016) S1400C Arm I (palbociclib) S1400C Arm II (CLOSED TO ACCRUAL 12/18/2015) S1400C Arm III (palbociclib) S1400D Arm I (AZD4547) (CLOSED TO ACCRUAL 04/12/2017) S1400D Arm II (CLOSED TO ACCRUAL 10/31/2016) S1400D Arm III (AZD4547) (CLOSED TO ACCRUAL 10/31/2016) S1400E Arm I (CLOSED TO ACCRUAL 11/2014) S1400E Arm II (CLOSED TO ACCRUAL 11/2014) S1400I Arm I (nivolumab, ipilimumab) S1400I Arm II (nivolumab) S1400G (talazoparib) S1400F (durvalumab, tremelimumab)

Name: Nivolumab

Description: Given IV

Type: Biological

S1400I Arm I (nivolumab, ipilimumab) S1400I Arm II (nivolumab)

Name: Palbociclib

Description: Given PO

Type: Drug

S1400C Arm I (palbociclib) S1400C Arm III (palbociclib)

Name: Pharmacological Study

Description: Correlative studies

Type: Other

S1400I Arm II (nivolumab) S1400G (talazoparib) S1400F (durvalumab, tremelimumab)

Name: Rilotumumab

Description: Given IV

Type: Biological

S1400E Arm I (CLOSED TO ACCRUAL 11/2014)

Name: Talazoparib

Description: Given PO

Type: Drug

S1400G (talazoparib)

Name: Taselisib

Description: Given PO

Type: Drug

S1400B Arm I (taselisib) (CLOSED TO ACCRUAL 12/12/2016) S1400B Arm III (taselisib) (CLOSED TO ACCRUAL 12/12/2016)

Name: Tremelimumab

Description: Given IV

Type: Biological

S1400F (durvalumab, tremelimumab)


Primary Outcomes

Description: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms.

Measure: Investigator-assessed progression-free survival as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II)

Time: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual

Description: Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median investigator-assessed progression-free survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified.

Measure: Investigator-assessed progression-free survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy vs standard therapy (Design #2,Phase III,Option for Biomarker-driven sub-studies)

Time: Up to 3 years

Description: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to investigator-assessed progression-free survival, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.

Measure: Less than 33% improvement in median investigator-assessed progression-free survival as defined as Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase III)

Time: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 18 months since completion of accrual

Description: The investigational therapy arm will be judged to have provided sufficient evidence to proceed to the Phase III component if the objective response rate is at least 25%. Response rates and associated confidence intervals will be calculated.

Measure: Objective response rate (confirmed and unconfirmed, complete and partial) (Design #2, Phase II, Option for Biomarker-driven Sub-studies)

Time: Up to 3 years

Description: Response rates and associated confidence intervals will be calculated.

Measure: Objective response rate (confirmed and unconfirmed, complete and partial) in patients treated with investigational non-match therapy with advanced stage refractory squamous cell carcinoma of the lung (Design #2, Option for Non-Match Sub-Studies)

Time: Up to 3 years

Description: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival, comparing the two treatment arms. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.

Measure: Overall survival (Design #1, Phase III)

Time: From date of sub-study registration (or date of screening registration if patient never enrolls in a sub-study) to date of death due to any cause, assessed up to 3 years

Description: The Brookmeyer-Crowley method will be used to calculate confidence intervals for median overall survival. A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified.

Measure: Overall survival in patients with advanced stage refractory squamous cell carcinoma of the lung randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies)

Time: Up to 3 years

Secondary Outcomes

Description: Estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median duration of response.

Measure: Duration of response among patients who achieve a complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies)

Time: Up to 3 years

Description: Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.

Measure: Frequency and severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies)

Time: Up to 3 years

Description: Descriptive data will be presented.

Measure: Investigator-assessed progression-free survival, censoring patients with symptomatic deterioration at the time of symptomatic deterioration (Design #1, Phase III)

Time: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Description: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to overall survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.

Measure: Overall survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies)

Time: Up to 3 years

Description: A stratified (using randomization stratification factors) log-rank test will be used to test the primary hypotheses related to progression free survival comparing the two treatment arms at the levels specified. A Cox PH model will be used to estimate the hazard ratios and associated confidence intervals.

Measure: Progression free survival with investigational therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies)

Time: Up to 3 years

Description: Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate. Response proportions will be compared using a 1-sided Fisher?s exact test at the 0.001 level.

Measure: Response rate (confirmed and unconfirmed) in patients with measurable disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 (Design #1, Phase II and III)

Time: Up to 3 years

Description: Analysis of response rates will be performed using a chi-square or Fisher?s exact test, as appropriate.

Measure: Response rates (confirmed and unconfirmed, complete and partial) among patients randomized to receive investigational therapy versus standard therapy (Design #2, Phase III, Option for Biomarker-driven Sub-studies)

Time: Up to 3 years

Description: Analysis of toxicities will be performed using a chi-square or Fisher?s exact test, as appropriate.

Measure: Severity of toxicities associated with investigational therapy versus standard therapy (Design #2, Phase II, Option for Biomarker-driven Sub-studies and Design #2, Option for Non-Match Sub-studies)

Time: Up to 3 years

Description: Analysis will be performed using a chi squared or Fisher?s exact test, as appropriate.

Measure: Toxicity frequencies, monitored using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Design #1, Phase II and III)

Time: Up to 3 years

Other Outcomes

Description: Descriptive data will be presented.

Measure: Screen success rate, monitored by the percentage of screened patients that register to a therapeutic sub-study

Time: Up to 3 years

Description: Descriptive data will be presented.

Measure: Treatment arm randomization acceptance rate, monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to (Design #1)

Time: Up to 3 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 7 SNPs

SNPs


1 S1400A

S1400A: (CLOSED TO ACCRUAL 12/18/2015) Patients with tumors that do not match one of the currently active drug-biomarker combinations or did not meet the eligibility requirements for that bio-marker driven sub-study are assigned to Arm I. Upon evidence of progression following discontinuation of 12 months of treatment, patients may restart treatment for up to 12 months with the same treatment guidelines followed during the initial 12-month treatment period (Arm III). --- S1400A ---


2 S1400C

S1400C (CLOSED TO ACCRUAL 09/01/2016): Patients with tumors positive for cyclin dependent kinase 4 (CDK4), cyclin D1 (CCND1), cyclin D2 (CCND2), and cyclin D3 (CCND3) are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, palbociclib, after disease progression on current treatment (Arm III). --- S1400C ---


3 S1400D

S1400D (CLOSED TO ACCRUAL 10/31/2016): Patients with tumors positive for fibroblast growth factor receptor (FGFR) 1, FGFR2, and FGFR3 are assigned to Arm I. Patients currently on Arm 2, docetaxel will be given the option to re-register to Arm 3, AZD4547, after disease progression on current treatment (Arm III). --- S1400D ---


4 S1400E

S1400E (CLOSED TO ACCRUAL 11/25/2014): Patients with tumors positive for met proto-oncogene (MET) are randomized to 1 of 2 treatment arms. --- S1400E ---


5 S1400F

S1400F: Patients with disease progression during or after prior anti-PD-1 or anti-PD-L1 antibody monotherapy as their most recent line of treatment receive durvalumab (IV over 60 minutes) and tremelimumab (IV over 60 minutes) on day 1 for courses 1-4 and durvalumab IV alone on day 1 of course 5 and subsequent courses until disease progression or unacceptable toxicity. --- S1400F ---


6 S1400G

S1400G: Patients with tumors positive for homologous recombination repair deficiency receive talazoparib PO daily on days 1-21. --- S1400G ---


7 S1400I

S1400I: Patients with tumors that do not match one of the currently active drug-biomarker combinations or did not meet the eligibility requirements for that bio-marker driven sub-study are randomized to 1 of 2 treatment arms. --- S1400I ---



HPO Nodes


HPO:
Carcinoma
Genes 11
PTEN CDKN1B APC MLH1 MSH2 FGFR3 KIT DKC1 RSPO1 STK11 NLRP1
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN