Abraxane in CIMP-High Colorectal and Small Bowel Adenocarcinomas

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01730586
• Collaborator: Celgene (Industry)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 45
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if abraxane can help to control colorectal and/or small bowel cancer. The safety of this drug will also be studied.

Abraxane is designed to block cancer cells from dividing, which may cause them to die.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Cancer of Gastrointestinal Tract	Drug: Abraxane	Phase 2

Detailed Description

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive the study drug in 21-day study cycles.

You will receive abraxane by vein over about 30 minutes on Day 1 of each cycle.

Study Visits:

On Day 1 of all cycles, the following tests and procedures will be performed:

• You will have a physical exam, including measurement of your weight and blood pressure.

• You will be asked about any drugs you may be taking and about any symptoms or side effects you may be having.

• Your performance status will be recorded.

• Blood (about 2 tablespoons) will be drawn for routine tests.

At the end of every 3rd cycle (Cycles 3, 6, 9) and so on:

°You will have a CT or MRI scan of your chest, abdomen, and pelvis to check the status of the disease. If at any point the scans show the disease appearing to get better, you will have another scan 2 cycles later.

Length of Treatment:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if you have intolerable side effects, if the study is stopped, or if you are unable to follow study instructions.

Your participation on the study will be over after the follow-up period.

End-of-Treatment Visit:

Within 10 days after you stop taking the study drug, you will have an end-of-treatment visit.

At this visit, the following tests and procedures will be performed:

• You will have a physical exam, including measurement of your weight and blood pressure.

• You will be asked about any drugs you may be taking and about any symptoms or side effects you may be having.

• Your performance status will be recorded.

• Blood (about 2 tablespoons) will be drawn for routine tests.

• If one has not been performed in the previous 4 weeks, you will have a CT or MRI scan of your chest, abdomen, and pelvis to check the status of the disease.

Follow-Up:

The study staff will ask about any symptoms or side effects you may be having during the 30 days after your last dose of the study drugs. The study staff may ask you by phone or at the time of a routine clinic visit. If the study staff contacts you by phone, the phone call should last about 15-30 minutes.

If you leave the study for any reason other than the disease getting worse, you will have a CT or MRI scan of your chest, abdomen, and pelvis to check the status of the disease every 12 weeks unless you start receiving other treatment.

The study staff will also review your medical records and/or contact you to check the status of the disease every 3 months after you stop receiving the study drug. If you are contacted by phone, each phone call should take about 5 minutes.

This is an investigational study. Abraxane is FDA approved and commercially available for the treatment of breast cancer. It is not FDA approved for the treatment of colorectal or small bowel cancer. The use of abraxane in patients with colorectal cancer or small bowel cancer is investigational.

Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Abraxane in CIMP-High Colorectal Adenocarcinomas and Small Bowel Adenocarcinomas
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abraxane Abraxane 220 mg/m2 administered by vein on Day 1. A cycle of therapy is defined as 21 days.	Drug: Abraxane; 220 mg/m2 administered by vein on Day 1. A cycle of therapy is defined as 21 days.; Other Names: Nab-Paclitaxel Paclitaxel (Protein-Bound) ABI-007

Outcome Measures

Primary Outcome Measures

1. Response Rate in CIMP-High Colorectal Cancer and Small Bowel Adenocarcinoma (SBA) [Assessed at 21 day cycle; Restaging done every 3 cycles]

   Evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1, 2009): Complete Response (CR): Disappearance all lesions including normalization of elevated tumor marker level; Pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): >30% decrease sum longest diameters (LD) of lesions reference baseline sum LD. Progressive Disease (PD): >20% increase (absolute increase >5 mm) in sum LD measured lesions references smallest sum LD, and appearance new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD. After a tumor demonstrates a tumor response (partial or complete), confirmation of the response obtained by a second evaluation to be performed 2 cycles later (+/- 1week) [second tumor assessment not <4 weeks from response observed]. Assessed via computed tomography (CT) of the chest, abdomen, and pelvis.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [Assessed at first cycle (21 days), up to 12 months]

   The length of time during and after the treatment a participant lives without disease progression. Time to progression functions estimated using the Kaplan-Meier method. Participants who drop out of the study included in the time to event data analysis as "censored data".

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patient must have histologically or cytologically confirmed colorectal adenocarcinoma or small bowel adenocarcinoma

2. Metastatic disease documented on diagnostic imaging studies with measurable disease per RECIST version 1.1.

3. Refractory disease defined as: a) prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-epidermal growth factor receptor (EGFR) therapy if Kirsten rat sarcoma (KRAS) wildtype for colorectal adenocarcinoma and; b) prior treatment with fluoropyrimidine and oxaliplatin for small bowel adenocarcinoma.

4. Colorectal adenocarcinoma patients must be known to have CpG island methylator phenotype. CIMP-high phenotype will be defined as hypermethylation at 2 or more of the 6 methylation-specific PCR markers (hMLH1, P16, P14, MINT1, MINT2, and MINT31).

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.

6. Adequate organ function including: a) Absolute neutrophil count (ANC) =/>1,500cells/mm^3; b) Platelets =/>100,000/ul; c) Hemoglobin >9.0 g/dL; d) Total bilirubin =/<1.5mg/dL In patients with known Gilbert's syndrome, direct bilirubin =/<1.5 x upper limit of normal (ULN) will be used as organ function criteria, instead of total bilirubin; e) AST and ALT < 2.5 x ULN; f) Alkaline phosphatase <2.5x ULN; g) Creatinine <1.5 gm/dL.

7. Negative serum or urine pregnancy test in women with childbearing potential (WOCBP) defined as not post-menopausal for 12 months or no previous surgical sterilization, within one week prior to initiation of treatment. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy.

8. A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom.

9. Patients must sign an Informed Consent and Authorization indicating that they are aware of the investigational nature of this study and the known risks involved.

10. Patient is =/>18 years of age on the day of consenting to the study.

Exclusion Criteria:

1. Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. In CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)".

2. Prior treatment with taxane therapy for either colorectal cancer or small bowel adenocarcinoma.

3. Chemotherapy or any other investigational agents within 14 days of first receipt of study treatment, or major surgery within 28 days of first receipt of study treatment, or palliative radiation within 7 days of first receipt of study treatment.

4. Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, uncontrolled diabetes, serious active or uncontrolled infection.

5. Pregnancy (positive pregnancy test) or lactation.

6. Patients with carcinomatous meningitis.

7. Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Celgene

Investigators

• Principal Investigator: Michael Overman, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01730586
• Other Study ID Numbers: 2012-0776; NCI-2013-00077
• First Posted: Nov 21, 2012
• Last Update Posted: Jan 18, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by M.D. Anderson Cancer Center: Colorectal Cancer; Cancer of Gastrointestinal Tract; CIMP-high Colorectal Adenocarcinoma; Small Bowel Adenocarcinomas; Colorectal; Small bowel cancer; Abraxane; Nab-Paclitaxel; Paclitaxel (Protein-Bound); ABI-007
• Additional relevant MeSH terms: Colorectal Neoplasms; Adenocarcinoma; Gastrointestinal Neoplasms; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	Recruitment Period: November 2012 to October 2015. All recruitment done at The University of Texas MD Anderson Cancer Center.

Arm/Group Title	Abraxane
Arm/Group Description	Abraxane 220 mg/m^2 intravenously on Day 1 of 21 day cycle.
Period Title: Overall Study
STARTED	34
COMPLETED	21
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Abraxane
Arm/Group Description	Abraxane 220 mg/m^2 intravenously on Day 1 of 21 day cycle.
Overall Participants	34
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	14 41.2%
Male	20 58.8%
Region of Enrollment (participants) [Number]
United States	34 100%
Colorectal Cancer Diagnosis (Count of Participants)
Small Bowel Adenocarcinoma (SBA)	13 38.2%
CIMP-high Colorectal Cancer (CRC)	21 61.8%

Outcome Measures

1. Primary Outcome

Title	Response Rate in CIMP-High Colorectal Cancer and Small Bowel Adenocarcinoma (SBA)
Description	Evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1, 2009): Complete Response (CR): Disappearance all lesions including normalization of elevated tumor marker level; Pathological lymph nodes reduction in short axis to <10 mm. Partial Response (PR): >30% decrease sum longest diameters (LD) of lesions reference baseline sum LD. Progressive Disease (PD): >20% increase (absolute increase >5 mm) in sum LD measured lesions references smallest sum LD, and appearance new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD. After a tumor demonstrates a tumor response (partial or complete), confirmation of the response obtained by a second evaluation to be performed 2 cycles later (+/- 1week) [second tumor assessment not <4 weeks from response observed]. Assessed via computed tomography (CT) of the chest, abdomen, and pelvis.
Time Frame	Assessed at 21 day cycle; Restaging done every 3 cycles

Outcome Measure Data

Analysis Population Description

In the CIMP-CRC arm 15 participants were considered efficacy evaluable [Of 21 treated, 6 participants were withdrawn due to toxicity (2) and due to clinical progression (4)], and three were not evaluable in SBA arm.

Arm/Group Title	CIMP-high Colorectal Cancer	Small Bowel Adenocarcinoma (SBA)
Arm/Group Description	Abraxane 220 mg/m^2 intravenously on Day 1 of 21 day cycle.	Abraxane 220 mg/m^2 intravenously on Day 1 of 21 day cycle.
Measure Participants	15	10
Complete Response	0 0%	0 NaN
Partial Response	0 0%	2 NaN
Stable Disease	3 8.8%	3 NaN
Progressive Disease	12 35.3%	5 NaN

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	The length of time during and after the treatment a participant lives without disease progression. Time to progression functions estimated using the Kaplan-Meier method. Participants who drop out of the study included in the time to event data analysis as "censored data".
Time Frame	Assessed at first cycle (21 days), up to 12 months

Outcome Measure Data

Analysis Population Description

For progression-free survival, the intent-to-treat analysis performed using all available participants.

Arm/Group Title	CIMP-high Colorectal Cancer	Small Bowel Adenocarcinoma
Arm/Group Description	Abraxane 220 mg/m^2 intravenously on Day 1 of 21 day cycle.	Abraxane 220 mg/m^2 intravenously on Day 1 of 21 day cycle.
Measure Participants	21	13
Median (95% Confidence Interval) [Months]	2.1	3.2

Adverse Events

Time Frame	Through Day 30 (Day 28 to Day 45 allowed) following the last dose of study drug or until resolution or stabilization of the toxicity or start of another treatment regimen, up to 3 years
Arm/Group Title	Abraxane
Arm/Group Description	Abraxane 220 mg/m^2 intravenously on Day 1 of 21 day cycle.
All Cause Mortality
	Abraxane
	Affected / at Risk (%)	# Events
Total	0/34 (0%)
Serious Adverse Events
	Abraxane
	Affected / at Risk (%)	# Events
Total	20/34 (58.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	3/34 (8.8%)
Gastrointestinal disorders
Small intestinal obstruction	6/34 (17.6%)
Jejunal obstruction	1/34 (2.9%)
Rectal pain	1/34 (2.9%)
Nausea	1/34 (2.9%)
General disorders
Fever	1/34 (2.9%)
Infections and infestations
Urinary tract infection	1/34 (2.9%)
Infection, Other - perirectal abcess	1/34 (2.9%)
Metabolism and nutrition disorders
Dehydration	1/34 (2.9%)
Psychiatric disorders
Confusion	1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/34 (2.9%)
Vascular disorders
Hypotension	2/34 (5.9%)
Other (Not Including Serious) Adverse Events
	Abraxane
	Affected / at Risk (%)	# Events
Total	34/34 (100%)
Blood and lymphatic system disorders
Abdominal distension	1/34 (2.9%)	1
Anemia	12/34 (35.3%)	15
Febrile neutropenia	3/34 (8.8%)	3
Endocrine disorders
Hypothyroidism	1/34 (2.9%)	1
Eye disorders
Blurred vision	4/34 (11.8%)	4
Eye disorders	1/34 (2.9%)	1
Gastrointestinal disorders
Abdominal pain	9/34 (26.5%)	18
Ascites	2/34 (5.9%)	2
Constipation	8/34 (23.5%)	12
Diarrhea	10/34 (29.4%)	19
Dry mouth	1/34 (2.9%)	1
Duodenal obstruction	1/34 (2.9%)	1
Dyspepsia	1/34 (2.9%)	1
Flatulence	2/34 (5.9%)	2
Gastroesophageal reflux disease	3/34 (8.8%)	3
Gastrointestinal disorders - (Other)	1/34 (2.9%)	3
Gastroparesis	1/34 (2.9%)	1
Ileus	2/34 (5.9%)	2
Mucositis oral	7/34 (20.6%)	8
Nausea	14/34 (41.2%)	24
Rectal pain	1/34 (2.9%)	4
Small intestinal obstruction	1/34 (2.9%)	2
Vomiting	8/34 (23.5%)	12
General disorders
Edema face	2/34 (5.9%)	2
Edema limbs	2/34 (5.9%)	2
Fatigue	21/34 (61.8%)	39
Fever	5/34 (14.7%)	5
Flu like symptoms	2/34 (5.9%)	2
Gait disturbance	1/34 (2.9%)	1
Localized edema	1/34 (2.9%)	1
Malaise	3/34 (8.8%)	4
Infections and infestations
Infections and infestations - (Other)	2/34 (5.9%)	4
Lung infection	3/34 (8.8%)	3
Sepsis	1/34 (2.9%)	1
Sinusitis	1/34 (2.9%)	1
Soft tissue infection	1/34 (2.9%)	1
Upper respiratory infection	1/34 (2.9%)	1
Urinary tract infection	2/34 (5.9%)	2
Investigations
Alanine aminotransferase increased	4/34 (11.8%)	4
Alkaline phosphatase increased	7/34 (20.6%)	7
Aspartate aminotransferase increased	4/34 (11.8%)	4
Blood bilirubin increased	3/34 (8.8%)	5
Creatinine increased	1/34 (2.9%)	1
Investigations - (Other)	1/34 (2.9%)	1
Neutrophil count decreased	5/34 (14.7%)	6
Platelet count decreased	5/34 (14.7%)	8
Weight loss	5/34 (14.7%)	5
White blood cell decreased	1/34 (2.9%)	1
Metabolism and nutrition disorders
Anorexia	9/34 (26.5%)	10
Dehydration	5/34 (14.7%)	6
Hyperuricemia	1/34 (2.9%)	1
Hypoalbuminemia	1/34 (2.9%)	2
Hypocalcemia	1/34 (2.9%)	1
Hypokalemia	3/34 (8.8%)	3
Hypomagnesemia	7/34 (20.6%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	12/34 (35.3%)	20
Back pain	3/34 (8.8%)	3
Bone pain	4/34 (11.8%)	6
Generalized muscle weakness	1/34 (2.9%)	1
Joint range of motion decreased	1/34 (2.9%)	1
Muscle weakness lower limb	2/34 (5.9%)	2
Myalgia	14/34 (41.2%)	28
Neck pain	1/34 (2.9%)	1
Pain	7/34 (20.6%)	12
Pain in extremity	2/34 (5.9%)	4
Nervous system disorders
Concentration impairment	1/34 (2.9%)	1
Dizziness	1/34 (2.9%)	1
Dysgeusia	5/34 (14.7%)	6
Headache	3/34 (8.8%)	5
Paresthesia	2/34 (5.9%)	2
Peripheral sensory neuropathy	9/34 (26.5%)	9
Presyncope	2/34 (5.9%)	2
Psychiatric disorders
Depression	1/34 (2.9%)	1
Insomnia	3/34 (8.8%)	5
Renal and urinary disorders
Acute kidney injury	2/34 (5.9%)	2
Urinary incontinence	2/34 (5.9%)	2
Urinary tract obstruction	1/34 (2.9%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/34 (2.9%)	1
Menorrhagia	1/34 (2.9%)	2
Pelvic pain	1/34 (2.9%)	1
Reproductive system and breast disorders - (Other)	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/34 (2.9%)	1
Cough	1/34 (2.9%)	1
Dyspnea	5/34 (14.7%)	7
Epistaxis	1/34 (2.9%)	1
Hoarseness	1/34 (2.9%)	1
Postnasal drip	1/34 (2.9%)	1
Skin and subcutaneous tissue disorders
Alopecia	26/34 (76.5%)	26
Hyperhidrosis	1/34 (2.9%)	1
Nail discoloration	2/34 (5.9%)	2
Pain of skin	1/34 (2.9%)	1
Palmar-plantar erythrodysesthesia syndrome	2/34 (5.9%)	2
Pruritus	2/34 (5.9%)	2
Rash acneiform	3/34 (8.8%)	3
Rash maculo-papular	6/34 (17.6%)	6
Skin and subcutaneous tissue disorders - (Other)	1/34 (2.9%)	2
Skin hyperpigmentation	1/34 (2.9%)	1
Vascular disorders
Flushing	4/34 (11.8%)	9
Hematoma	1/34 (2.9%)	1
Hot flashes	1/34 (2.9%)	1
Hypertension	2/34 (5.9%)	2
Hypotension	3/34 (8.8%)	4
Thromboembolic event	2/34 (5.9%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.