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Report for Clinical Trial NCT01304602

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer

This phase I trial will use the combination of irinotecan and BKM120 in patients with advanced colorectal cancer who have failed on or have become intolerant of at least one line of therapy for advanced colorectal cancer and who are candidates for irinotecan therapy.

NCT01304602 Colorectal Cancer
MeSH: Colorectal Neoplasms
HPO: Neoplasm of the large intestine

2 Interventions

Name: Irinotecan

Description: IV over 90 minutes on day 1 of each cycle (every 2 weeks) at the cohort assigned dose level

Type: Drug

Irinotecan + BKM120

Name: BKM120

Description: BKM120, oral, daily starting with cycle 1/day 2 at the cohort defined dose level

Type: Drug

Irinotecan + BKM120


Primary Outcomes

Description: The maximum tolerated dose will be defined as the dose level prior to the dose level in which dose-escalation was stopped based on dose-limiting toxicities (DLTs). DLTs are based on specific adverse events specified in the study protocol. DLTs will be assessed during the first two cycles of treatment (28 days total).

Measure: Maximum tolerated dose

Time: 28 days

Secondary Outcomes

Description: Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.

Measure: area under the plasma concentration versus time curve (AUC) of irinotecan

Time: up to 25.5 hours post dose of irinotecan

Description: Disease will be assessed at baseline and then every four cycles (8 weeks) by CT or MRI. Response will be assessed following RECIST criteria. Patients will be categorized as complete response, partial response, progressive disease, stable disease, or unknown.

Measure: Change in tumor size

Time: baseline, and every 8 weeks

Description: Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.

Measure: Peak Plasma Concentration (Cmax) of irinotecan

Time: up to 25.5 hours post-dose of irinotecan

Description: Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.

Measure: biological half-life of irinotecan

Time: up to 25.5 hours post dose of irinotecan

Description: The Cmax of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.

Measure: Peak Plasma Concentration (Cmax) of BKM120

Time: up to 25.5 hours post-dose of irinotecan

Description: The AUC of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.

Measure: area under the plasma concentration versus time curve (AUC) of BKM120

Time: up to 25.5 hours post dose of irinotecan

Description: The biological half life of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.

Measure: Biological half life of BKM120

Time: up to 25.5 hours post dose of irinotecan

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 P13K

If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Clinical manifestation of diabetes mellitus or steroid-induced diabetes mellitus - Impairment of GI function or disease that may significantly alter the absorption of BKM120; diarrhea ≥ grade 2 - Major surgery ≤ 4 weeks prior to starting study drug - Prior treatment with a P13K inhibitor; any hematopoietic colony-stimulating growth factors ≤ 2 weeks prior to starting study drug; corticosteroids ≤ 2 weeks prior to starting study drug; chemotherapy or targeted anticancer therapy ≤4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug; small molecule therapeutics (excluding monoclonal antibodies) ≤5 effective half-lives prior to starting study drug - Currently receiving medication that has the potential to prolong the QT interval or inducing Torsades de Pointes - chronic treatment with steroids or another immunosuppressive agent. --- P13K ---



HPO Nodes


HPO:
Neoplasm of the large intestine
Genes 120
FLCN SDHC MLH1 PMS2 APC EPCAM SDHC PALLD SRC BUB1 APC GREM1 NTHL1 PMS1 PTEN SDHB MSH6 APC KIT SDHD KRAS BMPR1A FAN1 CTNNB1 MSH3 POLD1 KRAS RNF43 KEAP1 DICER1 DLC1 BMPR1A MSH2 MSH6 PIK3CA CDKN2A FGFR3 BMPR1A MUTYH PIK3CA BMPR1A EP300 FOXE1 ENG SMAD7 AXIN2 CHEK2 MLH1 RPS20 BRCA1 RPS19 PRKAR1A APC GPR35 MLH1 AKT1 POLE SMAD4 KIT TP53 TRIP13 COL14A1 MDM2 SMAD4 POLE BRCA2 AKT1 MSH6 HABP2 NRAS MUTYH BUB1B DOCK8 TGFBR2 STK11 AXIN2 EPCAM BUB3 DCC AXIN2 TCF4 KLLN MSH2 APC TP53 SEC23B PTEN TGFBR2 SEMA4A POLD1 PIK3CA PDGFRA MINPP1 APC SH3KBP1 BMPR1A TP53 BUB1 AAGAB SMAD4 BMPR1A MST1 MLH3 MSH2 PALB2 FLCN SDHA PMS2 SDHB BUB1B MSH2 MLH1 CEP57 MLH3 TP53 PTPRJ PMS1 APC CDKN2A APC