Trial Outcomes & Findings for A Phase I Study of AZD6244 in Combination With Capecitabine and Radiotherapy in Locally Advanced Adenocarcinoma of the Rectum (NCT NCT01134601)

Last Updated: 2021-12-01

Results Overview

Maximum tolerable dose is defined as the dose level at which no more than 1 of 6 participants experience dose limiting toxicity (DLT) during treatment and the three weeks after completion. Examples of DLT is recurring and persistent Grade 3 diarrhea despite appropriate medical therapy, absolute neutrophil count \<500 for more than 5 days or neutropenic fever, Grade 3 thrombocytopenia, Grade 4 fatigue, and Grade 4 dermatitis acneiform rash.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

1 participants

Primary outcome timeframe

During treatment and within first 3 weeks after treatment

Results posted on

2021-12-01

Participant Flow

Participant milestones

Participant milestones
Measure	Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2 LEVEL 1 - Cycle = 49 days: AZD6244: 50 mg by mouth (PO) everyday (QD) Capecitabine: 825 mg/m\^2 by mouth (PO) Radiation Therapy Capecitabine AZD6244
Overall Study STARTED	1
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase I Study of AZD6244 in Combination With Capecitabine and Radiotherapy in Locally Advanced Adenocarcinoma of the Rectum

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2 n=1 Participants LEVEL 1 - Cycle = 49 days: AZD6244: 50 mg by mouth (PO) everyday (QD) Capecitabine: 825 mg/m\^2 by mouth (PO) Radiation Therapy Capecitabine AZD6244
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	53.8 years STANDARD_DEVIATION 0 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants

PRIMARY outcome

Timeframe: During treatment and within first 3 weeks after treatment

Population: This outcome measure was not done. As per the Cancer Therapy Evaluation Program (CTEP), this protocol has only enrolled one participant and it is unlikely that the study will be able to be completed successfully. CTEP slated the protocol to be administratively closed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-and post treatment

To evaluate the pharmacokinetics of AZD6244 in Combination with Capecitabine using logistic regression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-and post treatment

Changes in phosphorylated ERK (pERK) in peripheral blood mononuclear cells and tumor, and TGFa levels measured by flow cytometry.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.

Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2 n=1 Participants LEVEL 1 - Cycle = 49 days: AZD6244: 50 mg by mouth (PO) everyday (QD) Capecitabine: 825 mg/m\^2 by mouth (PO) Radiation Therapy Capecitabine AZD6244
Here is the Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: After treatment with the maximum tolerated dose

To obtain exploratory information regarding the pathologic response rate. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Complete Response is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: During treatment and within first 3 weeks after treatment

Examples of DLT is recurring and persistent Grade 3 diarrhea despite appropriate medical therapy, absolute neutrophil count \<500 for more than 5 days or neutropenic fever, Grade 3 thrombocytopenia, Grade 4 fatigue, and Grade 4 dermatitis acneiform rash.

Outcome measures

Outcome data not reported

Adverse Events

Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2 n=1 participants at risk LEVEL 1 - Cycle = 49 days: AZD6244: 50 mg by mouth (PO) everyday (QD) Capecitabine: 825 mg/m\^2 by mouth (PO) Radiation Therapy Capecitabine AZD6244
Gastrointestinal disorders Abdominal pain	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Investigations Activated partial thromboplastin time prolonged	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Investigations Alanine aminotransferase increased	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Blood and lymphatic system disorders Anemia	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Investigations Aspartate aminotransferase increased	100.0% 1/1 • Number of events 3 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Investigations CPK increased	100.0% 1/1 • Number of events 5 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Gastrointestinal disorders Dry mouth	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Skin and subcutaneous tissue disorders Dry skin	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
General disorders Fatigue	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Gastrointestinal disorders Flatulence	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Metabolism and nutrition disorders Hyperkalemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Metabolism and nutrition disorders Hypermagnesemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Metabolism and nutrition disorders Hypocalcemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Metabolism and nutrition disorders Hypokalemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Metabolism and nutrition disorders Hypophosphatemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Psychiatric disorders Insomnia	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Investigations Lymphocyte count decreased	100.0% 1/1 • Number of events 3 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Investigations Lymphocyte count increased	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Gastrointestinal disorders Nausea	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Gastrointestinal disorders Oral pain	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Reproductive system and breast disorders Pelvic pain	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Skin and subcutaneous tissue disorders Rash acneiform	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Skin and subcutaneous tissue disorders Rash maculo-papular	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, perianal erythema	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.
Investigations White blood cell decreased	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, and up to 30 days following the last dose of study drug, approximately 14 months and 26 days.

Additional Information

Dr. Deborah E. Citrin

National Cancer Institute

Phone: 301-496-5457

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place