Non-Metastatic Adenocarcinoma of the RectumPhase 1NCT01134601

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

A Phase 1 study testing Radiation Therapy, Capecitabine and AZD6244 in people with Non-Metastatic Adenocarcinoma of the Rectum, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Background: The investigational anti-cancer drug Selumetinib (AZD6244) prevents a protein found in rectal cancer from working properly, which may slow tumor growth and allow radiation and chemotherapy treatments to destroy more cancer cells. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Non-Metastatic Adenocarcinoma of the Rectum
What is being tested?: Radiation Therapy, Capecitabine and AZD6244
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: 1 siteUnited States
Study dates: 24 May 2010to 22 Oct 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must have histologically or cytologically confirmed locally advanced, non-metastatic adenocarcinoma of the rectum (clinical stage T3 anyN, T4 anyN, or AnyT N+).
Patients with recurrent adenocarcinoma of the rectum with no clinically evident distant disease will be eligible if they are deemed to have pelvic nodal metastases or disease extending through the muscularis of the rectum. These patients should be evaluated by a Radiation Oncologist, Medical Oncologist and Surgeon prior to enrolling on study to confirm anticipated resectability. These patients should not have received prior radiotherapy for management of their rectal cancer.
Age greater than or equal to 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky greater than or equal to 70%).
Patients must have normal organ and marrow function as defined below:
leukocytes greater than or equal to 3,000/mcL

Show all 16Show fewer

absolute neutrophil count greater than or equal to 1,500/mcL
platelets: greater than or equal to 100,000/mcL
total bilirubin: within normal institutional limits except for patients with Gilbert's who must have a direct bilirubin of less than 1.0 mg/dL
Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times the institutional upper limit of normal
creatinine within normal institutional limits
OR
-- creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for six months after the completion of radiation. Women of child-bearing potential must have a negative pregnancy test prior to entry. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Adequate contraception for male patients should be used for 6 months after irradiation.
Ability to understand and the willingness to sign a written informed consent document.
Willingness to sign a release of medical records pertaining to previous and future treatment for rectal cancer.

Who cannot join

Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or lack of recovery from adverse events due to agents administered more than 4 weeks earlier.
Patients may not be receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or other agents used in study.
Previous methyl ethyl ketone (MEK) inhibitor use.
Contraindications to radiotherapy to the pelvis such as inflammatory bowel disease or known genetic sensitivity to ionizing radiation such as ataxia telangiectasia.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Show all 17Show fewer

Patients with corrected QT interval (QTc) interval greater than 470 msecs or other factors that increase the risk of Q wave, T wave (QT) prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded.
Required use of a concomitant medication that can prolong the QT interval. A comprehensive list of agents with the potential to cause QTc prolongation can be found at http://www.arizonacert.org/medical-pros/drug-lists/drug-lists.htm.
Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy.
Known dihydropyrimidine dehydrogenase deficiency.
History of prior radiation to the pelvis
For patients with newly diagnosed rectal cancer, prior therapy for adenocarcinoma of the rectum with the exception of diverting colostomy if required to relieve obstruction (including chemotherapy).
Patients with recurrent rectal cancer may not have undergone prior radiotherapy for rectal adenocarcinoma or have received therapy for the recurrence with the exception of diverting colostomy if required to relieve obstruction.
History of myocardial infarction within the past 6 months or history of ventricular arrhythmia
Uncontrolled hypertension
Pregnant or lactating females are excluded

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Background:

The investigational anti-cancer drug Selumetinib (AZD6244) prevents a protein found in rectal cancer from working properly, which may slow tumor growth and allow radiation and chemotherapy treatments to destroy more cancer cells. Researchers are interested in determining whether AZD6244 can be used to improve treatment outcomes in individuals who have rectal cancer that has spread outside the rectum into the surrounding pelvis.

Objectives:

To determine safe and effective doses of AZD6244, along with radiation and chemotherapy, to treat rectal cancer.

Eligibility:

Individuals at least 18 years of age who have been diagnosed with rectal cancer that has spread outside the inner wall of the rectum or into lymph nodes in the pelvis.

Design:

Eligible participants will be screened with a physical examination, blood and tumor samples, and imaging studies.
Participants will receive AZD6244 twice a day by mouth for 1 full week (7 days) before starting radiation and chemotherapy and every week thereafter until the end of the radiation and chemotherapy treatment.
Participants will have radiation therapy daily, 5 days per week, for approximately 6 weeks.
Participants will receive chemotherapy (capecitabine) twice daily, 5 days per week, for approximately 6 weeks.
Approximately 4 to 8 weeks after completing the AZD6244, radiation, and chemotherapy treatment, participants may have surgery to remove any tumors and affected lymph nodes. This surgery is not part of the treatment delivered on this protocol.
Participants will have a follow-up exam 3 weeks after the end of treatment, every 3 months for the first year, and then in the second and third year after the end of treatment. These visits will involve a full medical examination and imaging studies.

Read the detailed description

Background:

Local recurrences of rectal cancer are morbid and difficult to manage effectively.
Colorectal cancers frequently harbor rat sarcoma (RAS) mutations and Epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) over-expression.
AZD6244 is an orally available selective, adenosine triphosphate uncompetitive inhibitor of methyl ethyl ketone (MEK)1/2 that sensitizes tumor cells to radiation in vitro and in vivo.

Objectives:

Primary

To define the maximum tolerable dose of AZD6244 Hyd-Sulfate delivered twice a day (BID), 7 days per week, in combination with radiation therapy (RT) and Capecitabine in patients with locally advanced adenocarcinoma of the rectum without distant metastases.
To define the dose-limiting toxicities and toxicity profile associated with administration of AZD6244 Hyd-Sulfate delivered BID, 7 days per week in combination with RT and Capecitabine

Secondary

To evaluate the pharmacokinetics of AZD6244 delivered alone and in combination with Capecitabine 825 mg/m(2) by mouth (PO) BID.
To obtain exploratory information regarding the pathologic response rate obtained after treatment with the maximum tolerated dose (MTD) of AZD6244 Hyd-Sulfate in combination with Capecitabine and 50.4 Gray (Gy) of RT.
To determine if changes in phosphorylated extracellular-signal regulated kinase (ERK) (pERK) in peripheral blood mononuclear cells correlates to changes in phosphorylated extracellular-signal regulated kinase (pERK) in rectal tumors in the setting of treatment with AZD6244.
To perform an exploratory analysis to determine if the presence of activating mutations in RAS or BRAF in tumor or changes in plasma transforming growth factor-alpha (TGFalpha) levels and tumor pERK/total ERK with AZD6244 treatment alone and after AZD6244 in combination with Capecitabine and RT predicts for down staging or pathologic response.

Eligibility:

Histologically or cytologically confirmed locally advanced, non-metastatic adenocarcinoma of the rectum (clinical stage T3AnyN, T4AnyN, or AnyTN+).
Age greater than or equal to 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Normal organ and marrow function.

Design:

All patients will receive 50.4 Gy of RT to the pelvis and rectal tumor delivered concurrently with Capecitabine and AZD6244. AZD6244 will be delivered BID daily, 7 days per week, in a dose escalated fashion. AZD6244 will begin one week prior to Capecitabine and RT and will conclude on the last day of Capecitabine and RT.
Capecitabine will be delivered at 825 mg/m(2) PO every 12 hours, 5 days per week, starting on the first day of RT and continuing until the last day of RT.
Biopsies of tumor tissue will be obtained prior to treatment, after one week of AZD6244, and after one week of AZD6244, RT, and Capecitabine for correlative assays.

Conditions: Non-Metastatic Adenocarcinoma of the Rectum
Being tested: Radiation Therapy, Capecitabine, AZD6244
Keywords: Rectal Cancer, Radiation Therapy, Capecitabine, AZD6244
Medical subject headings: Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Radiation TherapyProcedure or surgery
CapecitabineDrug
Also called Xeloda
AZD6244Drug
Also called Selumetinib

Study groups in NCT01134601
Study group	Role	What they receive
Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2	Experimental	LEVEL 1 - Cycle = 49 days: AZD6244: 50 mg by mouth (PO) everyday (QD) Capecitabine: 825 mg/m^2 by mouth (PO) Receives: Procedure: Radiation Therapy; Drug: Capecitabine; Drug: AZD6244

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Tolerable Dose of Selumetinib (AZD6244) Hyd-Sulfate in Combination With Radiation Therapy (RT) and Capecitabine in Participants With Locally Advanced Adenocarcinoma of the Rectum.
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.
Measured: During treatment and within first 3 weeks after treatment

Secondary outcomes (2)

Pharmacokinetics of Selumetinib (AZD6244) in Combination With Capecitabine
To evaluate the pharmacokinetics of AZD6244 in Combination with Capecitabine using logistic regression.
Measured: Pre-and post treatment
Changes in Phosphorylated ERK (pERK) in Peripheral Blood Mononuclear Cells and Tumor, and Transforming Growth Factor Alpha (TGFa) Levels
Changes in phosphorylated ERK (pERK) in peripheral blood mononuclear cells and tumor, and TGFa levels measured by flow cytometry.
Measured: Pre-and post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 May 201022 Oct 2012

First posted2 Jun 2010 (estimated)
Study start24 May 2010
Primary completion22 Oct 2012
Study completion22 Oct 2012

Why it stopped: As per 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.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Non-Metastatic Adenocarcinoma of the RectumStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01134601
Sponsor's protocol ID: 100132
Other IDs: 10-C-0132
Status last verified: Nov 2021
First submitted: 28 May 2010
Last updated: 1 Dec 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Davies BR, Logie A, McKay JS, Martin P, Steele S, Jenkins R, Cockerill M, Cartlidge S, Smith PD. AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther. 2007 Aug;6(8):2209-19. doi: 10.1158/1535-7163.MCT-07-0231.
PubMed 17699718
O'Neill E, Kolch W. Conferring specificity on the ubiquitous Raf/MEK signalling pathway. Br J Cancer. 2004 Jan 26;90(2):283-8. doi: 10.1038/sj.bjc.6601488.
PubMed 14735164
Wellbrock C, Ogilvie L, Hedley D, Karasarides M, Martin J, Niculescu-Duvaz D, Springer CJ, Marais R. V599EB-RAF is an oncogene in melanocytes. Cancer Res. 2004 Apr 1;64(7):2338-42. doi: 10.1158/0008-5472.can-03-3433.
PubMed 15059882

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
ABCSG R07 Rectal Cancer Registry
Rectal Cancer, Adenocarcinoma of Rectum
RecruitingPhase 2
Phase 2 Single-Arm Rectal Cancer Brachytherapy for Patients With Low-Lying Residual Adenocarcinoma After Total Neoadjuvant Therapy to Improve Organ Preservation Rates
Rectal Adenocarcinoma, Rectal Cancer
Recruiting
A Global, Integrated, Personalized, Stage-related, Multimodal Therapeutic Approach for Rectal Adenocarcinoma Based on Organ Sparing and Mininvasivity
Rectal Adenocarcinoma, Non Metastatic
Recruiting
Prospective Monocentric Study Evaluating the Circulating NK Cells Phenotype and the ImmunoScore® in Patients With Non Metastatic Rectal Cancer
Rectal Cancer, Non Metastatic Cancer

All Non-Metastatic Adenocarcinoma of the Rectum trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Study of AZD6244 in Combination With Capecitabine and Radiotherapy in Locally Advanced Adenocarcinoma of the Rectum
ClinicalTrials.gov ID: NCT01134601
Acronym / sponsor ID: 100132
Conditions: Non-Metastatic Adenocarcinoma of the Rectum
Keywords: Rectal Cancer, Radiation Therapy, Capecitabine, AZD6244
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: As per 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.
Enrolment: 1 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 24 May 2010 (actual)
Primary completion: 22 Oct 2012 (actual)
Study completion: 22 Oct 2012 (actual)
First posted: 2 Jun 2010 (estimated)
Results: Posted 1 Dec 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

The investigational anti-cancer drug Selumetinib (AZD6244) prevents a protein found in rectal cancer from working properly, which may slow tumor growth and allow radiation and chemotherapy treatments to destroy more cancer cells. Researchers are interested in determining whether AZD6244 can be used to improve treatment outcomes in individuals who have rectal cancer that has spread outside the rectum into the surrounding pelvis.

Objectives:

To determine safe and effective doses of AZD6244, along with radiation and chemotherapy, to treat rectal cancer.

Eligibility:

Individuals at least 18 years of age who have been diagnosed with rectal cancer that has spread outside the inner wall of the rectum or into lymph nodes in the pelvis.

Design:

Eligible participants will be screened with a physical examination, blood and tumor samples, and imaging studies.
Participants will receive AZD6244 twice a day by mouth for 1 full week (7 days) before starting radiation and chemotherapy and every week thereafter until the end of the radiation and chemotherapy treatment.
Participants will have radiation therapy daily, 5 days per week, for approximately 6 weeks.
Participants will receive chemotherapy (capecitabine) twice daily, 5 days per week, for approximately 6 weeks.
Approximately 4 to 8 weeks after completing the AZD6244, radiation, and chemotherapy treatment, participants may have surgery to remove any tumors and affected lymph nodes. This surgery is not part of the treatment delivered on this protocol.
Participants will have a follow-up exam 3 weeks after the end of treatment, every 3 months for the first year, and then in the second and third year after the end of treatment. These visits will involve a full medical examination and imaging studies.

Detailed description

Background:

Local recurrences of rectal cancer are morbid and difficult to manage effectively.
Colorectal cancers frequently harbor rat sarcoma (RAS) mutations and Epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) over-expression.
AZD6244 is an orally available selective, adenosine triphosphate uncompetitive inhibitor of methyl ethyl ketone (MEK)1/2 that sensitizes tumor cells to radiation in vitro and in vivo.

Objectives:

Primary

To define the maximum tolerable dose of AZD6244 Hyd-Sulfate delivered twice a day (BID), 7 days per week, in combination with radiation therapy (RT) and Capecitabine in patients with locally advanced adenocarcinoma of the rectum without distant metastases.
To define the dose-limiting toxicities and toxicity profile associated with administration of AZD6244 Hyd-Sulfate delivered BID, 7 days per week in combination with RT and Capecitabine

Secondary

To evaluate the pharmacokinetics of AZD6244 delivered alone and in combination with Capecitabine 825 mg/m(2) by mouth (PO) BID.
To obtain exploratory information regarding the pathologic response rate obtained after treatment with the maximum tolerated dose (MTD) of AZD6244 Hyd-Sulfate in combination with Capecitabine and 50.4 Gray (Gy) of RT.
To determine if changes in phosphorylated extracellular-signal regulated kinase (ERK) (pERK) in peripheral blood mononuclear cells correlates to changes in phosphorylated extracellular-signal regulated kinase (pERK) in rectal tumors in the setting of treatment with AZD6244.
To perform an exploratory analysis to determine if the presence of activating mutations in RAS or BRAF in tumor or changes in plasma transforming growth factor-alpha (TGFalpha) levels and tumor pERK/total ERK with AZD6244 treatment alone and after AZD6244 in combination with Capecitabine and RT predicts for down staging or pathologic response.

Eligibility:

Histologically or cytologically confirmed locally advanced, non-metastatic adenocarcinoma of the rectum (clinical stage T3AnyN, T4AnyN, or AnyTN+).
Age greater than or equal to 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
Normal organ and marrow function.

Design:

All patients will receive 50.4 Gy of RT to the pelvis and rectal tumor delivered concurrently with Capecitabine and AZD6244. AZD6244 will be delivered BID daily, 7 days per week, in a dose escalated fashion. AZD6244 will begin one week prior to Capecitabine and RT and will conclude on the last day of Capecitabine and RT.
Capecitabine will be delivered at 825 mg/m(2) PO every 12 hours, 5 days per week, starting on the first day of RT and continuing until the last day of RT.
Biopsies of tumor tissue will be obtained prior to treatment, after one week of AZD6244, and after one week of AZD6244, RT, and Capecitabine for correlative assays.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2	Experimental	Procedure: Radiation Therapy, Drug: Capecitabine, Drug: AZD6244LEVEL 1 - Cycle = 49 days: AZD6244: 50 mg by mouth (PO) everyday (QD) Capecitabine: 825 mg/m^2 by mouth (PO)

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

Patients must have histologically or cytologically confirmed locally advanced, non-metastatic adenocarcinoma of the rectum (clinical stage T3 anyN, T4 anyN, or AnyT N+).
Patients with recurrent adenocarcinoma of the rectum with no clinically evident distant disease will be eligible if they are deemed to have pelvic nodal metastases or disease extending through the muscularis of the rectum. These patients should be evaluated by a Radiation Oncologist, Medical Oncologist and Surgeon prior to enrolling on study to confirm anticipated resectability. These patients should not have received prior radiotherapy for management of their rectal cancer.
Age greater than or equal to 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky greater than or equal to 70%).
Patients must have normal organ and marrow function as defined below:

Key exclusion criteria (17 listed)

Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or lack of recovery from adverse events due to agents administered more than 4 weeks earlier.
Patients may not be receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or other agents used in study.
Previous methyl ethyl ketone (MEK) inhibitor use.
Contraindications to radiotherapy to the pelvis such as inflammatory bowel disease or known genetic sensitivity to ionizing radiation such as ataxia telangiectasia.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Radiation Therapy	Procedure or surgery	Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2
CapecitabineAlso: Xeloda	Drug	Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2
AZD6244Also: Selumetinib	Drug	Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2

Primary outcome

Maximum Tolerable Dose of Selumetinib (AZD6244) Hyd-Sulfate in Combination With Radiation Therapy (RT) and Capecitabine in Participants With Locally Advanced Adenocarcinoma of the Rectum.
Time frame: During treatment and within first 3 weeks after treatment
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.

2 secondary outcomes

Pharmacokinetics of Selumetinib (AZD6244) in Combination With Capecitabine
Time frame: Pre-and post treatment
Changes in Phosphorylated ERK (pERK) in Peripheral Blood Mononuclear Cells and Tumor, and Transforming Growth Factor Alpha (TGFa) Levels
Time frame: Pre-and post treatment

Results and safety

Results posted to the registry on 1 Dec 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2	1	1

Primary outcome: Maximum Tolerable Dose of Selumetinib (AZD6244) Hyd-Sulfate in Combination With Radiation Therapy (RT) and Capecitabine in Participants With Locally Advanced Adenocarcinoma of the Rectum.

Time frame: During treatment and within first 3 weeks after treatment

Population analysed: 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.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Selumetinib (AZD6244): 50 mg & Capecitabine: 825 mg/m^2	0 of 1 (0%)	1 of 1 (100%)	0 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 17699718Davies BR, Logie A, McKay JS, Martin P, Steele S, Jenkins R, Cockerill M, Cartlidge S, Smith PD. AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther. 2007 Aug;6(8):2209-19. doi: 10.1158/1535-7163.MCT-07-0231.
Background: PubMed 14735164O'Neill E, Kolch W. Conferring specificity on the ubiquitous Raf/MEK signalling pathway. Br J Cancer. 2004 Jan 26;90(2):283-8. doi: 10.1038/sj.bjc.6601488.
Background: PubMed 15059882Wellbrock C, Ogilvie L, Hedley D, Karasarides M, Martin J, Niculescu-Duvaz D, Springer CJ, Marais R. V599EB-RAF is an oncogene in melanocytes. Cancer Res. 2004 Apr 1;64(7):2338-42. doi: 10.1158/0008-5472.can-03-3433.
Individual participant dataSharing planned: No

Related trials for Non-Metastatic Adenocarcinoma of the Rectum

RecruitingObservational study
ABCSG R07 Rectal Cancer Registry
Rectal Cancer, Adenocarcinoma of Rectum
RecruitingPhase 2
Phase 2 Single-Arm Rectal Cancer Brachytherapy for Patients With Low-Lying Residual Adenocarcinoma After Total Neoadjuvant Therapy to Improve Organ Preservation Rates
Rectal Adenocarcinoma, Rectal Cancer
Recruiting
A Global, Integrated, Personalized, Stage-related, Multimodal Therapeutic Approach for Rectal Adenocarcinoma Based on Organ Sparing and Mininvasivity
Rectal Adenocarcinoma, Non Metastatic
Recruiting
Prospective Monocentric Study Evaluating the Circulating NK Cells Phenotype and the ImmunoScore® in Patients With Non Metastatic Rectal Cancer
Rectal Cancer, Non Metastatic Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Deborah E Citrin, M.D. principal investigator

National Cancer Institute (NCI)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Radiation Therapy, Capecitabine and AZD6244 in people with Non-Metastatic Adenocarcinoma of the Rectum, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerable Dose of Selumetinib (AZD6244) Hyd-Sulfate in Combination With Radiation Therapy (RT) and Capecitabine in Participants With Locally Advanced Adenocarcinoma of the Rectum. (time frame: During treatment and within first 3 weeks after treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01134601, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2021.