SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03779191

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Phase II, Open Label, Single Arm Trial of Alectinib in Combination With Bevacizumab in Untreated and Previously Treated Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) With Positive ALK Driver Mutation

Lung cancer remains the most lethal malignancy in both sexes around the world. It is estimated that lung cancer caused 234,030 deaths in the United States in 2016, accounting for 28% of all cancer-related deaths. In 2012 alone, a total of 6,697 deaths from lung cancer were registered in Mexico; this number exceeds the death toll from other common solid neoplasms (i.e., stomach, prostate, breast, and liver). In addition to its high incidence, lung cancer patients face a dismal prognosis, with an overall 5-year survival ranging from 5-16%. In the last two decades, the outlook for a subset of Non-small cell lung cancer (NSCLC) patients has shifted. Novel approaches have been able to identify that a significant number of patients present tumors with actionable mutations, opening the possibility of treatment with targeted therapies, which have increased survival outcomes in these patients. A number of specific therapies have been developed over the past decade, such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors. Additionally, treatment options for patients with NSCLC with actionable mutations has increased in the last two decades, with several third generation inhibitors available, which have different efficacy and tolerability profiles, nonetheless, global 5-year survival rates remain below 20%, which highlights the need to explore therapeutic combinations which might derive in greater long-term survival for this patient subgroup. Although encouraging data has been reported in terms of adding Bevacizumab to EGFR-TKIs, this scheme has not been explored for patients who have ALK-rearranged NSCLC and who are candidates for ALK-inhibitors. Currently, Alectinib has been shown to offer several advantages compared to first-generation ALK-TKIs, including a stronger ALK-inhibition, better outcomes in patients with Central Nervous System (CNS) involvement and longer duration of response. However, the addition of Bevacizumab to therapy with Alectinib in treatment naïve or previously treated NSCLC patients remains unexplored. Based on this data and the need to continue searching for safe and effective therapeutic options, a phase II, single arm trial assessing Alectinib in combination with Bevacizumab in untreated and previously treated patients with Advanced or Metastatic Non-Squamous ALK-rearranged NSCLC has been designed.

NCT03779191 ALK Gene Rearrangement Positive Non-Squamous Non-Small Cell Neoplasm of Lung
MeSH: Lung Neoplasms
HPO: Neoplasm of the lung

2 Interventions

Name: Alectinib

Description: Alectinib dosed 600 mg twice a day (BID) with meals until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Type: Drug

Intervention

Name: Bevacizumab

Description: Bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol

Type: Drug

Intervention


Primary Outcomes

Description: PFS based on response criteria according to RECIST 1.1 in untreated and previously treated patients with Advanced or metastatic ALK-rearranged Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab

Measure: Progression-free survival

Time: Through study completion, an average of 18 months

Secondary Outcomes

Description: To assess the ORR, based on response criteria according to RECIST 1.1, in untreated and previously treated patients with Advanced or Metastatic ALK-rearranged Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab.

Measure: Objective response rate

Time: 8 weeks

Description: To assess the brain ORR, based on response criteria according RECIST 1.1, in untreated and previously treated patients with Advanced or metastatic Non-Squamous NSCLC who receive treatment with Alectinib plus Bevacizumab.

Measure: Brain- ORR

Time: 8 weeks

Description: To assess the OS in untreated and previously treated patients with Advanced or metastatic Non-Squamous ALK-rearranged NSCLC who receive treatment with Alectinib plus Bevacizumab.

Measure: Overall survival

Time: Through study completion, an average of 18 months

Description: To assess the time since inclusion until developing brain metastases in untreated and previously treated patients with Advanced or metastatic Non-Squamous ALK-rearranged NSCLC who receive treatment with Alectinib plus Bevacizumab.

Measure: Time to developing brain metastases

Time: Through study completion, an average of 18 months

Description: To measure disease-related symptoms we will apply the Lung Cancer Symptom Scale (LCSS). The LCSS is designed as a disease-specific measure of quality of life particularly for use in clinical trials. It evaluates six major symptoms associated with lung mallignancies and their effect on overal symptomatic distress, functional activities, and global quality of life. The scale consists of two segments, one completed by the patient (9 items) and one completed by the health care professional (6 items). Scoring is assigned as follows: The patient scale consists of 9 visual analogue scales (100 mm horizontal line). Patient puts a mark on line to indicate intensity of response to the items in question (0 = lowest rating). The observer scale consists of a 5-point categorical scale (100=none; 75=mild; 50=moderate; 25=marked; 0=severe). The score is equal to the length of line marked by patient. An average of the aggregate score of all 9 items is the total score (0-100, 0= least symptom burden).

Measure: Disease-related symptom improvement

Time: 12 weeks since treatment start

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 L858R

Men who are sexually active with WOCBP, follow the instructions of birth control for a period of 90 days, plus the time required for the investigational drug is subject to five half-lives Exclusion Criteria: 1. Subjects with known EGFR mutations which are sensitive to available targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 [L858R] substitution mutations) are excluded. --- L858R ---

All patients┬┤ tumors contained either an exon 19 deletion or the amino acid substitution at position 858 in EGFR, from a leucine (L) to an arginine (R) (L858R) mutation. --- L858R ---



HPO Nodes


HPO:
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