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Report for Clinical Trial NCT01441128

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1, Open-Label, Dose Escalation Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of Combined Oral C-Met/ALK Inhibitor (PF-02341066) and Pan-Her Inhibitor (PF-0299804) in Patients With Advanced Non-Small Cell Lung Cancer

Background: - PF-02341066 and PF-00299804 are drugs that specifically target certain proteins that may be more active in cancer cells than normal cells, in particular in non-small cell lung cancer. Both drugs seem to be able to stop the growth of or kill cancer cells. Researchers want to combine them to see if they are a safe and effective treatment for advanced non-small cell lung cancer. Objectives: - To test the safety and effectiveness of PF-02341066 and PF-00299804 for advanced non-small cell lung cancer. Eligibility: - Individuals at least 18 years of age with advanced non-small cell lung cancer that has not responded to standard treatments. Design: - Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and imaging studies. Heart and lung function tests and an eye exam may also be given. - The first cycle of treatment will be 28 days. Every cycle after the first will be 21 days. Participants may have up to 17 cycles of treatment. - Participants will take both study drugs as tablets. Twelve hours after the first dose, participants will take only the PF-02341066. This dose schedule will remain the same throughout the study. - Participants will be monitored with frequent blood and urine tests and imaging studies. Tumor biopsies will be taken as needed. Those in the study will keep a diary to record any symptoms or side effects of taking the study drugs. - After 17 cycles of treatment, or after stopping the study drugs early for any other reason, participants will have a final followup visit.

NCT01441128 Carcinoma, Non-Small Cell Lung Adenocarcinoma Carcinoma, Squamous Cell Carcinoma, Large Cell
MeSH: Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Adenocarcinoma Carcinoma, Squamous Cell Carcinoma, Large Cell
HPO: Carcinoma Neoplasm of the lung Non-small cell lung carcinoma Squamous cell carcinoma

2 Interventions

Name: PF-02341066/PF-00299804

Description: Combined PF-02341066 and PF-00299804

Type: Drug

Arm 1 Arm 2

Name: PF-02341066/PF-00299804

Description: Single Agent PF-00299804 followed by Combined PF-02341066 and PF-00299804

Type: Drug

Arm 1 Arm 2


Primary Outcomes

Measure: Overall safety profile of combined PF 02341066 plus PF 00299804 including adverse events (AE), as defined and graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], and first cycle Dose Limiting Tox...

Time: 18 months

Secondary Outcomes

Measure: Plasma concentrations and pharmacokinetic (PK) parameters of PF 02341066 and PF 00299804 including AUCtau, Cmax, Ctrough, Tmax, and CLss/F

Time: 18 months

Measure: Clinical activity of combined PF 02341066 plus PF 00299804 including objective response (OR) and stable disease (SD) as defined by RECIST version 1.1, duration of response (DR) and progression free survival (PFS).

Time: 18 months

Measure: Biomarkers in tumor and blood that are potentially predictive for drug activity: for example, KRAS mutations, EGFR mutations (eg, T790M), EGFR and HER2 amplifications, c Met amplification and mutations, ALK, PTEN and PIK3A status in tumor biopsi...

Time: 12 months

Measure: Pharmacodynamic biomarkers in tumor biopsies (e.g., phospho c Met, c Met, EGFR, phospho EGFR) and in blood (e.g., HGF and s Met) that are modulated following drug exposure.

Time: 12 months

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 T790M

Biomarkers in tumor and blood that are potentially predictive for drug activity: for example, KRAS mutations, EGFR mutations (eg, T790M), EGFR and HER2 amplifications, c Met amplification and mutations, ALK, PTEN and PIK3A status in tumor biopsi.... null. --- T790M ---

- Despite the dramatic initial response to gefitinib and erlotinib, about 50% of NSCLC tumors develop resistance due to secondary activating mutations in EGFR itself, including the EGFR T790M gatekeeper mutation, and more than 20% of acquired resistance is due to an increase in mesenchymal-epithelial transition factor (c-Met) signaling. --- T790M ---

- There is evidence from a limited number of tumors from patients with acquired resistance to EGFR-TKIs that both T790M and cMET resistance mechanisms can occur in the same patient at different metastatic sites and even in different fractions of the same lesion. --- T790M ---

- Tumors with acquired resistance to erlotinib and gefitinib might be vulnerable to a combination of PF-00299804 a second generation EGFR TKI which is also an inhibitor of T790M mutation, and PF-02341066 which is an inhibitor of c- Met/Hepatocyte Growth Factor Receptor (HGFR). --- T790M ---



HPO Nodes


HPO:
Carcinoma
Genes 16
POLE MSH2 DKC1 SMARCA4 NLRP1 POLD1 CDKN1B MLH1 RSPO1 FGFR3 BCL10 APC STK11 PTEN APC KIT
Neoplasm of the lung
Genes 61
REST GPC3 WT1 HPGD BRAF PIK3CA TP53 TRIM28 RB1 TRIP13 SLCO2A1 AKT1 CASP8 KRAS TSC1 POU6F2 EWSR1 PRKN LMNA NAB2 TERT TSC2 SLC22A18 BRCA2 PPP2R1B STAT6 STK11 MUC5B ERBB2 TSC2 MBTPS2 BAP1 TSC2 DICER1 PDGFRB PERP EGFR TSC1 DIS3L2 NOTCH3 KEAP1 DICER1 DICER1 WT1 TSC1 C11ORF95 IRF1 CYP2A6 WRN RELA WT1 PTEN SFTPC SFTPA2 ERCC6 TRPV3 TP53 H19 TRIM28 FASLG MAP3K8
Non-small cell lung carcinoma
Genes 3
TP53 TP53 BAP1
Squamous cell carcinoma
Genes 79
COL7A1 WNT10A CDKN2A GJB6 FDPS LZTS1 GTF2H5 TERT NLRP1 ERCC5 NUTM1 ERCC2 RSPO1 LAMA3 TMC8 CTSC ING1 RECQL4 GJB2 ERCC2 TGFBR2 ERCC4 LAMC2 LAMB3 MPLKIP TARS1 ERCC3 XPC DOCK8 BLM NTHL1 TYR PSENEN WRAP53 GTF2E2 IL7 RNF6 SLC17A9 TNFRSF10B DKC1 POLH RECQL4 BLM BRD4 KRT5 TMC6 TERC ERCC2 SASH1 WNT10A MC1R CIB1 SLC45A2 MVD WRN KRT14 DDB2 RNF113A DCC FERMT1 TYR COL7A1 ERCC3 ERCC3 COL7A1 MMP1 COL7A1 GJB2 SLX4 MMP1 LMNA MVK TINF2 WWOX GJB2 OCA2 CIB1 POLH STAT1