Investigating Cabozantinib in Patients With Refractory Metastatic Colorectal Cancer

• Sponsor: Academic Thoracic Oncology Medical Investigators Consortium (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03542877
• Collaborator: University of Colorado, Denver (Other)
• Enrollment: 44
• Locations: 10
• Arm: 1
• Actual Duration (Months): 45.2
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study seeks to use Cabozantinib to treat those with Metastatic Colorectal Cancer who have not previously responded to treatment.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: Oral Tablet: Cabozantinib	Phase 2

Detailed Description

This is a phase II clinical trial that seeks to use Cabozantinib to treat those with Metastatic Colorectal Cancer who have not previously responded to treatment. This study is a two stage study that will first measure (up to) 16 patients' progression free survival (PFS). Stage two will, again, measure PFS, but in a population (up to) 28 patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Single-Arm, Two-Stage Phase II Study Investigating Cabozantinib in Patients With Refractory Metastatic Colorectal Cancer
• Actual Study Start Date: Jun 1, 2018
• Actual Primary Completion Date: Oct 19, 2020
• Actual Study Completion Date: Mar 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Cabozantinib Patients will be enrolled to take 60mg of cabozantinib, by mouth, once a day, every day, for 12 weeks. If less than three patients have Progression Free Survival (PFS) lasting at least 12 weeks, the study will be terminated.	Drug: Oral Tablet: Cabozantinib; Patients will take 60mg cabozantinib, by mouth, once daily, every day for 12 weeks. This medication should be taken on an empty stomach. Patients should not eat 2 hours before or 1 hour after taking cabozantinib. Only water is permitted during this 3 hour time frame.; Other Names: Cometriq Cabometyx

Outcome Measures

Primary Outcome Measures

1. 12-Week Progression Free Survival [This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.]

   A patient is classified as progression-free if s/he is assessed as not having progressive disease (PD) as defined per RECIST 1.1 criteria at either the 12-week assessment or after having at least 11 weeks of treatment for subjects without the 12-week assessment. Censored patients (i.e. those who have not progressed but who are missing a 12-week assessment) are not included in the analysis. Subjects who didn't have the 12-week assessment but who had clinical progression were included and considered to have progressed. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. 12-Week Progression-Free Survival by RAS Mutation Status [This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.]

   This has the same outcome measure description as the primary analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

2. 12-Week Progression-Free Survival by PIK3CA Mutation Status [This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.]

   This has the same outcome measure description as the primary analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

3. Progression-Free Survival (PFS) [Study start date to study end date, or death, whichever comes first, up to 24 months]

   Progression-free survival will be defined as the time from administration of the initial dose of cabozantinib to evidence of radiographic progression as defined by RECIST criteria or death from any cause without evidence of disease progression, whichever occurs first. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

4. Progression-Free Survival (PFS) by RAS Mutation Status [Study start date to study end date, or death, whichever comes first, up to 24 months]

   This has the same outcome measure description as the PFS analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

5. Progression-Free Survival (PFS) by PIK3CA Mutation Status [Study start date to study end date, or death, whichever comes first, up to 24 months]

   This has the same outcome measure description as the PFS analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

6. Response Rate in Patients With CRC Treated With Cabozantinib [Study start date to study end date, or death, whichever comes first, up to 24 months]

   *A patient is classified as a responder if s/he is assessed as having complete response or partial response (CR or PR) at the time of any assessment, where CR and PR are defined per RECIST 1.1 criteria.

7. Overall Survival (OS) in Patients With CRC Treated With Cabozantinib [Study start date to study end date, or death, whichever comes first, up to 24 months]

   Overall Survival will be defined as the time from administration of the initial dose of cabozantinib until death from any cause.

8. Overall Survival (OS) by RAS Mutation Status [Study start date to study end date, or death, whichever comes first, up to 24 months]

   This has the same outcome measure description as the OS analysis.

9. Overall Survival (OS) by PIK3CA Mutation Status [Study start date to study end date, or death, whichever comes first, up to 24 months]

   This has the same outcome measure description as the OS analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The subject has a histologic or cytologic diagnosis of colorectal adenocarcinoma that is metastatic or unresectable and is refractory to or progressed (or relapsed) following a fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab; prior epidermal growth factor inhibitor therapy is required for patients with left-sided, RAS wild-type tumors; prior FDA-approved PD-1 inhibitor therapy is required for patients with MSI-H colorectal cancer. Prior regorafenib or TAS-102 treatment is not required.

2. Measurable disease per RECIST 1.1 as determined by the investigator.

3. The subject has had an assessment of all known disease sites e.g., by computerized tomography (CT) scan and/or magnetic resonance imaging (MRI) within 28 days before the first dose of cabozantinib.

4. The subject is ≥ 18 years old on the day of consent.

5. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Recovery to baseline or ≤ Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.

7. Adequate archival frozen or fixed tissue available from primary or metastatic site for genotypic analysis (at least 15 unstained slides and/or tumor block).

8. The subject has organ and marrow function and laboratory values as follows within 7 days before the first dose of cabozantinib:

9. ANC ≥ 1500/mm3 without colony stimulating factor support;

10. Platelets ≥ 100,000/mm3;

11. Hemoglobin ≥ 9 g/dL;

12. Bilirubin ≤ 1.5 x ULN. For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL;

13. Serum albumin ≥ 2.8 g/dl;

14. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used:

• Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72);

• Female: Multiply above result by 0.85;

1. ALT and AST ≤ 3.0 x ULN;

2. Lipase < 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis;

3. UPCR ≤ 1;

4. Serum phosphorus, calcium, magnesium and potassium ≥ LLN.

5. The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.

6. Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control or practice abstinence during the study and for 4 months after the last dose of study drug(s).

Exclusion Criteria:

1. The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment;

2. Prior treatment with cabozantinib;

3. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible;

4. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment. Note: Subjects with prostate cancer currently receiving LHRH or GnRH agonists may be maintained on these agents;

5. The subject has received any other type of investigational agent within 28 days before the first dose of study treatment;

6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment;

7. The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment;

8. Concomitant anticoagulation at therapeutic doses with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel); Note: Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (< 1 mg/day), and low dose, low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 12 weeks before randomization, and who have had no complications from a thromboembolic event or the anticoagulation regimen. ;

9. The subject has experienced any of the following:

10. clinically-significant GI bleeding within 6 months before the first dose of study treatment;

11. hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment;

12. any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.

13. The subject has radiographic evidence of cavitating pulmonary lesion(s);

14. The subject has tumor invading or encasing any major blood vessels;

15. The subject has evidence of clinically significant bleeding from tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib;

16. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

1. Cardiovascular disorders including: i. Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening; ii. Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment; iii. Any history of congenital long QT syndrome; iv. Any of the following within 6 months before the first dose of study treatment:

• unstable angina pectoris;

• clinically-significant cardiac arrhythmias;

• stroke (including transient ischemic attack (TIA), or other ischemic event);

• myocardial infarction;

• thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (eg, vena cava filter) are not eligible for this study).

1. GI disorders particularly those associated with a high risk of perforation or fistula formation including: i. Active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before randomization, Note: Complete healing of an intra-abdominal abscess must be confirmed prior to randomization c. Other clinically significant disorders that would preclude safe study participation;

1. Major surgery within 12 weeks before the first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment. Minor surgery (including uncomplicated tooth extractions) within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible;

2. QTcF > 500 msec within 1 month before the first dose of study treatment:

1. Three ECGs must be performed for eligibility determination. If the average of these three consecutive results for QTcF is ≤ 500 msec, the subject meets eligibility in this regard.

1. Pregnant or lactating females;

2. Inability to swallow intact tablets;

3. Previously identified allergy or hypersensitivity to components of the study treatment formulations;

4. Diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona	Tucson	Arizona	United States	85724
2	Kenneth Norris Jr. Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	Universtiy of Colorado Denver	Aurora	Colorado	United States	80045
4	Lone Tree Health Center	Lone Tree	Colorado	United States	80124
5	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
6	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
7	Jefferson Abington Hospital	Abington	Pennsylvania	United States	19001
8	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
9	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
10	Swedish Medical Center	Seattle	Washington	United States	98122

Sponsors and Collaborators

• Academic Thoracic Oncology Medical Investigators Consortium
• University of Colorado, Denver

Investigators

• Principal Investigator: Wells Messersmith, MD, University of Colorado, Denver

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 27, 2018

More Information

Publications

None provided.

• Responsible Party: Academic Thoracic Oncology Medical Investigators Consortium
• ClinicalTrials.gov Identifier: NCT03542877
• Other Study ID Numbers: 18-0021.cc
• First Posted: May 31, 2018
• Last Update Posted: Jul 15, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Academic Thoracic Oncology Medical Investigators Consortium: Cabozantinib; Progression Free Survival; Metastatic Colorectal Cancer; Tumor
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Arm/Group Title	Oral Cabozantinib
Arm/Group Description	Patients will be enrolled to take 60mg of cabozantinib, by mouth, once a day, every day, for 12 weeks. If less than three patients have Progression Free Survival (PFS) lasting at least 12 weeks, the study will be terminated. Oral Tablet: Cabozantinib: Patients will take 60mg cabozantinib, by mouth, once daily, every day for 12 weeks. This medication should be taken on an empty stomach. Patients should not eat 2 hours before or 1 hour after taking cabozantinib. Only water is permitted during this 3 hour time frame.
Period Title: Overall Study
STARTED	44
COMPLETED	23
NOT COMPLETED	21

Baseline Characteristics

Arm/Group Title	Oral Cabozantinib
Arm/Group Description	Patients will be enrolled to take 60mg of cabozantinib, by mouth, once a day, every day, for 12 weeks. If less than three patients have Progression Free Survival (PFS) lasting at least 12 weeks, the study will be terminated. Oral Tablet: Cabozantinib: Patients will take 60mg cabozantinib, by mouth, once daily, every day for 12 weeks. This medication should be taken on an empty stomach. Patients should not eat 2 hours before or 1 hour after taking cabozantinib. Only water is permitted during this 3 hour time frame.
Overall Participants	44
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	33 75%
>=65 years	11 25%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (23)
Sex/Gender, Customized (Count of Participants)
Female	13 29.5%
Male	30 68.2%
Unknown	1 2.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 13.6%
Not Hispanic or Latino	37 84.1%
Unknown or Not Reported	1 2.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.3%
White	38 86.4%
More than one race	0 0%
Unknown or Not Reported	5 11.4%
Region of Enrollment (participants) [Number]
United States	44 100%

Outcome Measures

1. Primary Outcome

Title	12-Week Progression Free Survival
Description	A patient is classified as progression-free if s/he is assessed as not having progressive disease (PD) as defined per RECIST 1.1 criteria at either the 12-week assessment or after having at least 11 weeks of treatment for subjects without the 12-week assessment. Censored patients (i.e. those who have not progressed but who are missing a 12-week assessment) are not included in the analysis. Subjects who didn't have the 12-week assessment but who had clinical progression were included and considered to have progressed. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.

Outcome Measure Data

Analysis Population Description

40 of the 44 subjects were in the analysis population. 3 subjects were not included because they didn't have treatment response data, and 1 subject was not included because that subject didn't reach at least week 11 (and didn't have PD).

Arm/Group Title	Oral Cabozantinib
Arm/Group Description	Patients will be enrolled to take 60mg of cabozantinib, by mouth, once a day, every day, for 12 weeks. If less than three patients have Progression Free Survival (PFS) lasting at least 12 weeks, the study will be terminated. Oral Tablet: Cabozantinib: Patients will take 60mg cabozantinib, by mouth, once daily, every day for 12 weeks. This medication should be taken on an empty stomach. Patients should not eat 2 hours before or 1 hour after taking cabozantinib. Only water is permitted during this 3 hour time frame.
Measure Participants	40
Count of Participants [Participants]	18 40.9%

2. Secondary Outcome

Title	12-Week Progression-Free Survival by RAS Mutation Status
Description	This has the same outcome measure description as the primary analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.

Outcome Measure Data

Analysis Population Description

This population was the same as the population for the primary analysis

Arm/Group Title	RAS Mutant	RAS Wild Type
Arm/Group Description	Subjects who were RAS mutant.	Subjects with wild type RAS mutation status
Measure Participants	22	18
Count of Participants [Participants]	7 15.9%	11 NaN

3. Secondary Outcome

Title	12-Week Progression-Free Survival by PIK3CA Mutation Status
Description	This has the same outcome measure description as the primary analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.

Outcome Measure Data

Analysis Population Description

All subjects in the primary analysis who had data regarding their PIK3CA mutation status.

Arm/Group Title	PIK3CA Mutant	PIK3CA Wild Type
Arm/Group Description	Subjects who were PIK3CA mutant.	Subjects with wild type PIK3CA mutation status.
Measure Participants	6	22
Count of Participants [Participants]	3 6.8%	11 NaN

4. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Progression-free survival will be defined as the time from administration of the initial dose of cabozantinib to evidence of radiographic progression as defined by RECIST criteria or death from any cause without evidence of disease progression, whichever occurs first. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Study start date to study end date, or death, whichever comes first, up to 24 months

Outcome Measure Data

Analysis Population Description

3 of the 44 study subjects were not included in this analysis population because they didn't have treatment response data.

Arm/Group Title	Oral Cabozantinib
Arm/Group Description	Patients will be enrolled to take 60mg of cabozantinib, by mouth, once a day, every day, for 12 weeks. If less than three patients have Progression Free Survival (PFS) lasting at least 12 weeks, the study will be terminated. Oral Tablet: Cabozantinib: Patients will take 60mg cabozantinib, by mouth, once daily, every day for 12 weeks. This medication should be taken on an empty stomach. Patients should not eat 2 hours before or 1 hour after taking cabozantinib. Only water is permitted during this 3 hour time frame.
Measure Participants	41
Median (95% Confidence Interval) [Weeks]	13

5. Secondary Outcome

Title	Progression-Free Survival (PFS) by RAS Mutation Status
Description	This has the same outcome measure description as the PFS analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Study start date to study end date, or death, whichever comes first, up to 24 months

Outcome Measure Data

Analysis Population Description

3 of the 44 study subjects were not included in this analysis population because they didn't have treatment response data.

Arm/Group Title	RAS Mutant	RAS Wild Type
Arm/Group Description	Subjects who were RAS mutant.	Subjects with wild type RAS mutation status
Measure Participants	23	18
Median (95% Confidence Interval) [Weeks]	12	21

6. Secondary Outcome

Title	Progression-Free Survival (PFS) by PIK3CA Mutation Status
Description	This has the same outcome measure description as the PFS analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Study start date to study end date, or death, whichever comes first, up to 24 months

Outcome Measure Data

Analysis Population Description

All subjects in the PFS secondary analysis who had data regarding their PIK3CA mutation status.

Arm/Group Title	PIK3CA Mutant	PIK3CA Wild Type
Arm/Group Description	Subjects who were PIK3CA mutant.	Subjects with wild type PIK3CA mutation status.
Measure Participants	7	22
Median (95% Confidence Interval) [Weeks]	26	20

7. Secondary Outcome

Title	Response Rate in Patients With CRC Treated With Cabozantinib
Description	*A patient is classified as a responder if s/he is assessed as having complete response or partial response (CR or PR) at the time of any assessment, where CR and PR are defined per RECIST 1.1 criteria.
Time Frame	Study start date to study end date, or death, whichever comes first, up to 24 months

Outcome Measure Data

Analysis Population Description

This analysis population was the same as described for the primary analysis.

Arm/Group Title	Oral Cabozantinib
Arm/Group Description	Patients will be enrolled to take 60mg of cabozantinib, by mouth, once a day, every day, for 12 weeks. If less than three patients have Progression Free Survival (PFS) lasting at least 12 weeks, the study will be terminated. Oral Tablet: Cabozantinib: Patients will take 60mg cabozantinib, by mouth, once daily, every day for 12 weeks. This medication should be taken on an empty stomach. Patients should not eat 2 hours before or 1 hour after taking cabozantinib. Only water is permitted during this 3 hour time frame.
Measure Participants	40
Count of Participants [Participants]	1 2.3%

8. Secondary Outcome

Title	Overall Survival (OS) in Patients With CRC Treated With Cabozantinib
Description	Overall Survival will be defined as the time from administration of the initial dose of cabozantinib until death from any cause.
Time Frame	Study start date to study end date, or death, whichever comes first, up to 24 months

Outcome Measure Data

Analysis Population Description

All 34 subjects with follow-up data (i.e. data in the 'dataset_survival_follow_up.xlsx' table) were included in the analysis.

Arm/Group Title	Oral Cabozantinib
Arm/Group Description	Patients will be enrolled to take 60mg of cabozantinib, by mouth, once a day, every day, for 12 weeks. If less than three patients have Progression Free Survival (PFS) lasting at least 12 weeks, the study will be terminated. Oral Tablet: Cabozantinib: Patients will take 60mg cabozantinib, by mouth, once daily, every day for 12 weeks. This medication should be taken on an empty stomach. Patients should not eat 2 hours before or 1 hour after taking cabozantinib. Only water is permitted during this 3 hour time frame.
Measure Participants	34
Median (95% Confidence Interval) [Weeks]	36

9. Secondary Outcome

Title	Overall Survival (OS) by RAS Mutation Status
Description	This has the same outcome measure description as the OS analysis.
Time Frame	Study start date to study end date, or death, whichever comes first, up to 24 months

Outcome Measure Data

Analysis Population Description

All 34 subjects with follow-up data (i.e. data in the 'dataset_survival_follow_up.xlsx' table) were included in the analysis.

Arm/Group Title	RAS Mutant	RAS Wild Type
Arm/Group Description	Subjects who were RAS mutant.	Subjects with wild type RAS mutation status
Measure Participants	19	15
Median (95% Confidence Interval) [Weeks]	30	45

10. Secondary Outcome

Title	Overall Survival (OS) by PIK3CA Mutation Status
Description	This has the same outcome measure description as the OS analysis.
Time Frame	Study start date to study end date, or death, whichever comes first, up to 24 months

Outcome Measure Data

Analysis Population Description

All subjects in the secondary OS analysis who had data regarding their PIK3CA mutation status.

Arm/Group Title	PIK3CA Mutant	PIK3CA Wild Type
Arm/Group Description	Subjects who were PIK3CA mutant.	Subjects with wild type PIK3CA mutation status.
Measure Participants	5	17
Median (95% Confidence Interval) [Weeks]	92	36

Adverse Events

Time Frame	45 months
Arm/Group Title	Oral Cabozantinib
Arm/Group Description	Patients will be enrolled to take 60mg of cabozantinib, by mouth, once a day, every day, for 12 weeks. If less than three patients have Progression Free Survival (PFS) lasting at least 12 weeks, the study will be terminated. Oral Tablet: Cabozantinib: Patients will take 60mg cabozantinib, by mouth, once daily, every day for 12 weeks. This medication should be taken on an empty stomach. Patients should not eat 2 hours before or 1 hour after taking cabozantinib. Only water is permitted during this 3 hour time frame.
All Cause Mortality
	Oral Cabozantinib
	Affected / at Risk (%)	# Events
Total	5/44 (11.4%)
Serious Adverse Events
	Oral Cabozantinib
	Affected / at Risk (%)	# Events
Total	20/44 (45.5%)
Blood and lymphatic system disorders
Disseminated Intravascular Coagulation	1/44 (2.3%)	1
Thrombocytopenia	1/44 (2.3%)	1
Gastrointestinal disorders
Abdominal Pain	1/44 (2.3%)	1
Acute Pancreatitis	1/44 (2.3%)	1
Bowel Perforation	1/44 (2.3%)	1
Constipation	1/44 (2.3%)	2
Duodenal fistula	1/44 (2.3%)	1
GI bleed	2/44 (4.5%)	2
nausea	1/44 (2.3%)	1
Bowel Obstruction	1/44 (2.3%)	2
Vomiting	1/44 (2.3%)	2
General disorders
Acute Cerebrovascular Accident	1/44 (2.3%)	1
Back Pain	1/44 (2.3%)	1
Dehydration	1/44 (2.3%)	1
difficulty speaking	1/44 (2.3%)	1
Disease Progression	2/44 (4.5%)	2
Failure to Thrive	1/44 (2.3%)	1
Progressed Malignant Neoplasm	1/44 (2.3%)	1
Injury, poisoning and procedural complications
Spinal Fracture	1/44 (2.3%)	1
Renal and urinary disorders
Acute Renal Failure	1/44 (2.3%)	1
Severe Complicated Bilateral Pyelonephritis	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Cavitating Pulmonary Nodules	1/44 (2.3%)	1
dyspnea	2/44 (4.5%)	2
Hypoxia	1/44 (2.3%)	1
Lung infection	2/44 (4.5%)	2
Pleural Effusion	3/44 (6.8%)	4
Pneumonia	1/44 (2.3%)	1
Pulmonary Embolism	1/44 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Oral Cabozantinib
	Affected / at Risk (%)	# Events
Total	43/44 (97.7%)
Blood and lymphatic system disorders
Alanine aminotransferase increased	2/44 (4.5%)	2
Alkaline phosphatase increased	7/44 (15.9%)	8
alanine aminotransferase increase	7/44 (15.9%)	10
Amylase increased	3/44 (6.8%)	4
Anemia	7/44 (15.9%)	8
Aspartate aminotransferase increased	9/44 (20.5%)	19
Edema	9/44 (20.5%)	12
Hyperkalemia	1/44 (2.3%)	1
Hypertension	15/44 (34.1%)	31
Elevated Creatinine	4/44 (9.1%)	5
Hypokalemia	8/44 (18.2%)	11
thrombocytopenia	8/44 (18.2%)	9
Elevated Liver Function Test	1/44 (2.3%)	1
Lactate Increased	1/44 (2.3%)	1
Hyperamylasemia	5/44 (11.4%)	7
Bilirubin Increased	6/44 (13.6%)	12
Hyperlipasemia	4/44 (9.1%)	5
Hypocalcemia	1/44 (2.3%)	1
Hyponatremia	2/44 (4.5%)	2
Lymphocytopenia	3/44 (6.8%)	3
Hypernatremia	1/44 (2.3%)	1
Hypoalbuminemia	4/44 (9.1%)	4
Deep Vein Thrombosis	1/44 (2.3%)	1
Leukopenia	6/44 (13.6%)	9
Ascites	1/44 (2.3%)	1
Thrombocytopenia	1/44 (2.3%)	1
Tumor Lysis Syndrome	1/44 (2.3%)	1
Neutropenia	2/44 (4.5%)	2
Cardiac disorders
Elevated troponin	1/44 (2.3%)	1
Tachycardia	1/44 (2.3%)	1
Hypotension	2/44 (4.5%)	3
bradycardia	1/44 (2.3%)	1
Syncope	1/44 (2.3%)	1
Conduction Disorder	1/44 (2.3%)	1
Endocrine disorders
Hypothyroidism	10/44 (22.7%)	11
TSH elevated	4/44 (9.1%)	4
Hyperglycemia	3/44 (6.8%)	4
Gastrointestinal disorders
Abdominal Pain	16/44 (36.4%)	19
Abdominal Distension	1/44 (2.3%)	2
Acid Reflux	3/44 (6.8%)	3
Constipation	14/44 (31.8%)	15
Diarrhea	23/44 (52.3%)	33
Bloating	2/44 (4.5%)	2
vomiting	12/44 (27.3%)	17
fecal impaction	1/44 (2.3%)	1
Reflux	9/44 (20.5%)	9
Flatulence	5/44 (11.4%)	5
Distended Abdomen	2/44 (4.5%)	3
General disorders
Alopecia	3/44 (6.8%)	3
Anorexia	16/44 (36.4%)	26
Hearing Loss	1/44 (2.3%)	1
Nausea	17/44 (38.6%)	19
sinusitis	1/44 (2.3%)	1
Fatigue	28/44 (63.6%)	48
chest pain	3/44 (6.8%)	3
sore throat	6/44 (13.6%)	7
hoarse	4/44 (9.1%)	4
Chills	4/44 (9.1%)	4
fever	8/44 (18.2%)	9
forgetfulness	3/44 (6.8%)	3
Abdominal Tenderness	1/44 (2.3%)	1
Pain	17/44 (38.6%)	38
Ache	6/44 (13.6%)	9
Weakness	2/44 (4.5%)	2
Decreased Appetite	2/44 (4.5%)	2
Congestion	3/44 (6.8%)	4
Bleeding gums	1/44 (2.3%)	1
Malnutrition	1/44 (2.3%)	1
Dizziness	7/44 (15.9%)	9
Dysgeusia	7/44 (15.9%)	7
Cough	7/44 (15.9%)	9
Gait Disturbance	2/44 (4.5%)	2
Dysesthesia	2/44 (4.5%)	2
Hypersomnia	1/44 (2.3%)	1
Blurred vision	3/44 (6.8%)	3
Dental Caries	2/44 (4.5%)	2
Migraine	2/44 (4.5%)	2
Change in Hair Color	2/44 (4.5%)	3
Dehydration	1/44 (2.3%)	1
Neurological Changes	1/44 (2.3%)	1
Diaphoresis	1/44 (2.3%)	1
Hepatobiliary disorders
Jaundice	1/44 (2.3%)	1
Infections and infestations
Sepsis	2/44 (4.5%)	2
Infection	1/44 (2.3%)	1
Tonsilitis	1/44 (2.3%)	1
Pancreatitis	1/44 (2.3%)	1
Laryngitis	1/44 (2.3%)	1
Injury, poisoning and procedural complications
Spinal Fracture	1/44 (2.3%)	1
Wound bleeding	1/44 (2.3%)	1
Metabolism and nutrition disorders
Weight loss	14/44 (31.8%)	19
Weight Gain	1/44 (2.3%)	1
Musculoskeletal and connective tissue disorders
Cramping	10/44 (22.7%)	11
Jaw pain	1/44 (2.3%)	2
Myalgia	2/44 (4.5%)	2
Nervous system disorders
Neuropathy	7/44 (15.9%)	7
Neuropathy	2/44 (4.5%)	2
Psychiatric disorders
Mood alteration	2/44 (4.5%)	2
Renal and urinary disorders
Proteinuria	12/44 (27.3%)	20
Hematuria	7/44 (15.9%)	10
Hyperuricemia	1/44 (2.3%)	1
Urinary Retention	2/44 (4.5%)	2
Elevated Urine Protein Creatinine Ratio	2/44 (4.5%)	4
Increased Creatinine	1/44 (2.3%)	1
Urine Discoloration	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/44 (2.3%)	1
Dyspnea	5/44 (11.4%)	5
Skin and subcutaneous tissue disorders
Acne	3/44 (6.8%)	3
Mouth Sores	2/44 (4.5%)	2
Mouth Sensitivity	1/44 (2.3%)	1
Skin sensitivity	3/44 (6.8%)	3
Rash	6/44 (13.6%)	9
palmar-plantar erythrodysesthesia	14/44 (31.8%)	35
Mucositis	5/44 (11.4%)	5
Ulcer	1/44 (2.3%)	1
Xerostomia	4/44 (9.1%)	4
epistaxis	1/44 (2.3%)	1
hypopigmentation	2/44 (4.5%)	2
Dry Skin	3/44 (6.8%)	3
Pruritus	6/44 (13.6%)	6
Numbness of skin	1/44 (2.3%)	1
Burning mouth syndrom	1/44 (2.3%)	1
Bruising	1/44 (2.3%)	1
Vascular disorders
Hypertention	3/44 (6.8%)	8
Shock	1/44 (2.3%)	1

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.