Study of Enzastaurin With 5-Fluorouracil/Leucovorin (5-FU/LV) Plus Bevacizumab as Maintenance Regimen Following First Line Therapy for Metastatic Colon Cancer

Phase 2

Completed

Interventions: Drug: Placebo
Drug: Enzastaurin
Drug: Leucovorin (LV)
Drug: 5-fluorouracil (5-FU)
Drug: Bevacizumab (Bev)

Brief Summary: This study will evaluate the addition of enzastaurin to 5-FU (5-fluorouracil)/LV (leucovorin) plus bevacizumab in the maintenance of best response obtained with 6 cycles of first-line therapy consisting of 5-FU/LV + oxaliplatin (FOLFOX) or 5-FU/LV + irinotecan (FOLFIRI), plus bevacizumab in patients with Metastatic Colorectal Cancer.

Recruitment & Eligibility

Inclusion Criteria

Histologic diagnosis of locally advanced or metastatic colorectal cancer (CRC) that is not curable. The histology types to be included are adenocarcinoma, mucinous adenocarcinoma, signet ring, and undifferentiated. Patients with neuroendocrine carcinomas will be excluded.
Received 6 cycles (3 months [12 weeks]) of first-line therapy with FOLFOX or FOLFIRI, plus bevacizumab for metastatic CRC. Patients have received at least 5 cycles with bevacizumab. Patients who received 6 cycles of first-line therapy with FOLFOX or FOLFIRI, plus bevacizumab for recurrent CRC that has relapsed at least 12 months after completion of adjuvant therapy will also be included. All standard FOLFOX (FOLFIRI) regimens given on a biweekly schedule will be permitted; however, 21-day regimens will not be allowed.
No more than 4 weeks may pass between the end of first-line therapy (that is, Day 14 of Cycle 6) and randomization.
Documented evidence of tumor response of complete response (CR), partial response (PR), or stable disease (SD) by computed tomography (CT) scan or magnetic resonance imaging (MRI). Confirmation of response is not required.

Exclusion Criteria

Are unable to swallow tablets.
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Have known central nervous system metastases.
Are receiving concurrent administration of any other antitumor therapy.
Patients who have significant heart, liver, kidney, or psychiatric disease or have an active infection

Arm && Interventions

Group	Intervention	Description
Enzastaurin + 5-FU/LV + Bev	Leucovorin (LV)	5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with enzastaurin
Placebo + 5-FU/LV + Bev	Bevacizumab (Bev)	5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with placebo
Enzastaurin + 5-FU/LV + Bev	Bevacizumab (Bev)	5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with enzastaurin
Enzastaurin + 5-FU/LV + Bev	5-fluorouracil (5-FU)	5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with enzastaurin
Placebo + 5-FU/LV + Bev	Placebo	5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with placebo
Placebo + 5-FU/LV + Bev	Leucovorin (LV)	5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with placebo
Placebo + 5-FU/LV + Bev	5-fluorouracil (5-FU)	5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with placebo
Enzastaurin + 5-FU/LV + Bev	Enzastaurin	5-fluorouracil/leucovorin (5-FU/LV) plus bevacizumab (Bev) in combination with enzastaurin

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Randomization to measured progressive disease or death up to 17.2 months	PFS was defined as the time from randomization to the first observation of disease progression or death due to any cause. Progressive disease was determined using a modified version of Response Evaluation Criteria in Solid Tumor (RECIST) Assessment and was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to disease progression was censored at the date of death if death was due to other cause.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) From Start of First Line Therapy	Start of first line therapy (approximately 3 months prior to randomization) to date of death from any cause up to 27 months post randomization	OS was the duration from first line therapy to death due to any cause. For participants who are alive, OS is censored at the last contact.
Number of Participants With Adverse Events (AEs)	Randomization up to 17.2 months	A summary of serious and all other non-serious AEs is located in the Reported Adverse Event module.
Overall Survival (OS)	Randomization up to 22.8 months	OS was the duration from enrollment to death due to any cause. For participants who are alive, OS is censored at the last contact.
PFS From Start of First Line Therapy	Start of first line therapy to measured progressive disease or death up to 24 months	PFS was defined as the time from first line therapy to the first observation of disease progression or death due to any cause. Progressive disease was determined using a modified version of RECIST Assessment and was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to disease progression was censored at the date of death if death was due to other cause.

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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San Juan, Puerto Rico