AZD0530 (NSC 735464) in Treating Patients With Previously Treated Metastatic Colon Cancer or Rectal Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00397878
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 60
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial is studying how well AZD0530 works in treating patients with previously treated metastatic colon cancer or rectal cancer. AZD0530 may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer	Drug: saracatinib; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the progression-free survival (PFS) at 4 months in metastatic colorectal carcinoma patients receiving daily doses of AZD0530.

SECONDARY OBJECTIVES:

1. Evaluate the objective response rate (RR) and overall survival (OS) of patients with metastatic colorectal cancer who are treated with AZD0530.

2. In patients who consent, both blood and tissue samples will be collected for laboratory correlates. Assess in a preliminary manner the association between correlative markers and the potential downstream effects of AZD0530 on IL-8, VEGF, specific Src-regulated markers in focal adhesions, adherens junctions, and angiogenesis on clinical outcome in pre- and post-treatment tumor samples.

OUTLINE:

Patients receive oral AZD0530 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of AZD0530 (NSC 735464) in Patients With Previously Treated Metastatic Colorectal Cancer
• Actual Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (saracatinib) Patients receive oral AZD0530 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: saracatinib; Given orally; Other Names: AZD0530 ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Median Progression Free Survival (PFS) [Time from start of treatment to time of progression, up to 4 months]

   Time period of metastatic colorectal patients with one previous chemotherapy treatment for metastatic disease who are alive and progression free after commencing the experimental therapy. A 95% posterior credible intervals used.

Secondary Outcome Measures

1. Overall Survival [Up to 5 years]

   Number of participants who survived up to 5 years

2. Time to Progression [within 54 days]

   Number of participants who progressed on treatment within less than or equal to 2 cycles (cycle=28 days; within 54 days PD).

Other Outcome Measures

1. Pre- and Post-treatment Expression Values for Each Biological Correlate [Up to 2 weeks]

   Statistical significance of the associations assessed using a nonparametric Sign Test performed on the difference of the post-treatment and pre-treatment values. A two-sided .05 significance level to be used.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic

• Patients must have measurable disease, defined (per RECIST criteria) as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or >= 10 mm with spiral CT scan

• Patients must have received one and only one prior chemotherapy regimen for metastatic colorectal cancer; patients may have received biologic therapy (e.g., bevacizumab) in combination with chemotherapy as part of their prior chemotherapy

• ECOG performance status 0-2

• Absolute neutrophil count (ANC) >= 1,500/mcL

• Platelets >= 100,000/mcL

• Hemoglobin >= 9 g/dL

• Total bilirubin =< 1.5 x institutional ULN

• AST(SGOT)/ALT(SGPT) =< 3.0 x institutional ULN

• Creatinine within normal institutional limits OR estimated CrCl (Cockcroft-Gault) or 24 hr urine collection of >= 50 mL/min

• The effects of AZD0530 on the developing human fetus at the recommended therapeutic dose are unknown; however, AZD0530 has been shown to cause gross fetal malformations and to negatively impact embryo fetal survival in rats; for this reason and because many tyrosine kinase inhibitors are known to be teratogenic, 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 up to 30 days following removal from the study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; women of child-bearing potential will have serum beta-Hcg levels drawn up to 7 days prior to receiving study treatment

• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD0530, breastfeeding should be discontinued if the mother is treated with AZD0530

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study registration or those who have not recovered from treatment related adverse events > grade 1 (except for neuropathy [ies] which may be =< grade 2) due to agents administered more than 4 weeks earlier

• Use of specifically prohibited CYP3A4-active agents or substances are not permitted during protocol treatment, and patients who must continue treatment with these agents are not eligible; prohibited drugs should be discontinued seven (7) days or 5 half-lives (whichever is the longer time period) prior to the administration of the first dose of AZD0530 and for 7 days or 5 half-lives (which ever is the longer time period) following discontinuation of AZD0530

• Patients may not be receiving any other investigational agents

• Patients with greater than +1 proteinuria on two consecutive readings taken no less than 24 hours apart are ineligible

• Patients with QTc prolongation (defined as a QTc interval greater than or equal to 480 msecs) are ineligible

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring parenteral antibiotics at the time of registration), cardiac disease NYHA class III or IV, unstable angina pectoris, unstable cardiac arrhythmia or tachycardia (heart rate >= 100 beats per minute), poorly controlled hypertension (systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg)

• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow AZD0530 tablets are excluded

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

• Pregnant women are excluded from this study because AZD0530 has the potential for teratogenic or abortifacient effects as shown by the gross fetal malformation and effects on embryofetal survival seen in reproductive toxicity studies in the rat

• Patients with a history of another primary malignancy within the last 5 years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix

• Patient who are known to be HIV-positive are ineligible because of the potential for pharmacokinetic interactions with AZD0530 and antiretroviral therapy (HAART)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Cathy Eng, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00397878
• Other Study ID Numbers: NCI-2013-00067; NCI-2013-00067; CDR0000512970; MDA-2005-0977; NCI-7569; 2005-0977; 7565; N01CM62202; P30CA016672
• First Posted: Nov 10, 2006
• Last Update Posted: Aug 20, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Recurrence; Saracatinib

Study Results

Participant Flow

Recruitment Details	Recruitment Period: November 16, 2006 to April 08, 2008. Recruitment done at University of Texas (UT) MD Anderson Cancer Center.

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Oral AZD0530 175 mg once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Oral AZD0530 175 mg once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Participants	10
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	4 40%
Male	6 60%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival (PFS)
Description	Time period of metastatic colorectal patients with one previous chemotherapy treatment for metastatic disease who are alive and progression free after commencing the experimental therapy. A 95% posterior credible intervals used.
Time Frame	Time from start of treatment to time of progression, up to 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Oral AZD0530 175 mg once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	10
Median (Full Range) [weeks]	7.9

2. Secondary Outcome

Title	Overall Survival
Description	Number of participants who survived up to 5 years
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Oral AZD0530 175 mg once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	10
Count of Participants [Participants]	6 60%

3. Secondary Outcome

Title	Time to Progression
Description	Number of participants who progressed on treatment within less than or equal to 2 cycles (cycle=28 days; within 54 days PD).
Time Frame	within 54 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Oral AZD0530 175 mg once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	10
Count of Participants [Participants]	10 100%

4. Other Pre-specified Outcome

Title	Pre- and Post-treatment Expression Values for Each Biological Correlate
Description	Statistical significance of the associations assessed using a nonparametric Sign Test performed on the difference of the post-treatment and pre-treatment values. A two-sided .05 significance level to be used.
Time Frame	Up to 2 weeks

Outcome Measure Data

Analysis Population Description

No patients consented to optional tissue analysis.

Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Oral AZD0530 175 mg once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	0

Adverse Events

Time Frame	Adverse events collected while participant was receiving treatment and up to 30 days after the last dose of treatment. Total study period was from January 10, 2007 to February 25, 2009.
Arm/Group Title	Treatment (Saracatinib)
Arm/Group Description	Oral AZD0530 175 mg once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	9/10 (90%)
Blood and lymphatic system disorders
Lymphocyte count decreased	1/10 (10%)	1
White blood cell decreased	1/10 (10%)	1
Gastrointestinal disorders
Abdominal pain	1/10 (10%)	1
Dehydration	1/10 (10%)	1
Nausea	2/10 (20%)	2
Small intestinal perforation	1/10 (10%)	1
General disorders
Death NOS	6/10 (60%)	10
Fatigue	1/10 (10%)	1
Infections and infestations
Sepsis	1/10 (10%)	1
Metabolism and nutrition disorders
Blood bilirubin increased	1/10 (10%)	1
Hypoalbuminemia	1/10 (10%)	1
Hypocalcemia	1/10 (10%)	1
Hyponatremia	2/10 (20%)	3
Hypophosphatemia	4/10 (40%)	6
Musculoskeletal and connective tissue disorders
Fibrosis deep connective tissue	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Lung Infection	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Saracatinib)
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anemia	9/10 (90%)	12
Lymphocyte count decreased	1/10 (10%)	2
Neutrophil count decreased	1/10 (10%)	1
Platelet count decreased	4/10 (40%)	4
White blood cell decreased	1/10 (10%)	3
Cardiac disorders
Hypertension	3/10 (30%)	3
Endocrine disorders
Hypothyroidism	1/10 (10%)	1
Eye disorders
Watering eyes	2/10 (20%)	2
Gastrointestinal disorders
Anorexia	5/10 (50%)	5
Diarrhea	5/10 (50%)	6
Abdominal distension	2/10 (20%)	2
Abdominal pain	6/10 (60%)	6
Constipation	5/10 (50%)	8
Flatulence	1/10 (10%)	2
Gastritis	2/10 (20%)	2
Hemorrhoidal hemorrhage	1/10 (10%)	1
Mucositis oral	1/10 (10%)	1
Nausea	5/10 (50%)	8
Proctitis	1/10 (10%)	1
Rectal hemorrhage	1/10 (10%)	1
Vomiting	3/10 (30%)	6
General disorders
Fatigue	10/10 (100%)	16
Fever	3/10 (30%)	3
Headache	1/10 (10%)	1
Tumor pain	2/10 (20%)	2
Weight loss	2/10 (20%)	2
Hepatobiliary disorders
Alanine aminotransferase increased	1/10 (10%)	1
Aspartate aminotransferase increased	6/10 (60%)	7
Blood bilirubin increased	3/10 (30%)	3
Immune system disorders
Immune system disorders	2/10 (20%)	2
Infections and infestations
Urinatry Tract Infections	5/10 (50%)	6
Elevated Blood Counts (Investigations)	5/10 (50%)	6
Metabolism and nutrition disorders
Alkaline phosphatase increased	8/10 (80%)	12
Acidosis	1/10 (10%)	1
Cholesterol high	3/10 (30%)	3
Creatine phosphokinase (CPK) increased	1/10 (10%)	1
Creatinine increased	2/10 (20%)	2
Hemoglobinuria	1/10 (10%)	1
Hyperglycemia	7/10 (70%)	8
Hyperkalemia	3/10 (30%)	4
Hyperuricemia	1/10 (10%)	1
Hypoalbuminemia	2/10 (20%)	3
Hypocalcemia	3/10 (30%)	3
Hypokalemia	1/10 (10%)	1
Hyponatremia	2/10 (20%)	5
Hypophosphatemia	6/10 (60%)	11
Proteinuria	5/10 (50%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	2/10 (20%)	2
Back Pain	2/10 (20%)	2
Extraocular muscle paresis	1/10 (10%)	1
Myalgia	2/10 (20%)	2
Pain	1/10 (10%)	1
Nervous system disorders
Peripheral sensory neuropathy	7/10 (70%)	7
Psychiatric disorders
Anxiety	2/10 (20%)	2
Depression	2/10 (20%)	2
Insomnia	2/10 (20%)	2
Renal and urinary disorders
Urinary frequency/retention	2/10 (20%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/10 (10%)	2
Epistaxis	1/10 (10%)	1
Pleural effusion	1/10 (10%)	1
Repiratory, Running Nose	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Alopecia	2/10 (20%)	2
Nail loss	2/10 (20%)	2
Palmar-plantar erythrodysesthesia syndrome	1/10 (10%)	1
Rash acneiform	3/10 (30%)	5
Skin hyperpigmentation	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.