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Colorectal CancerPhase 2NCT03542877

Investigating Cabozantinib in Patients With Refractory Metastatic Colorectal Cancer

A Phase 2 study testing Oral Tablet: Cabozantinib in people with Colorectal Cancer, run by Academic Thoracic Oncology Medical Investigators Consortium at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Colorectal Cancer
What is being tested?
Oral Tablet: Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
10 sitesUnited States
Study dates
1 Jun 2018to 7 Mar 2022
Phase
Phase 2
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

  • 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.
  • Measurable disease per RECIST 1.1 as determined by the investigator.
  • 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.
  • The subject is ≥ 18 years old on the day of consent.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • 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.
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  • Adequate archival frozen or fixed tissue available from primary or metastatic site for genotypic analysis (at least 15 unstained slides and/or tumor block).
  • The subject has organ and marrow function and laboratory values as follows within 7 days before the first dose of cabozantinib:
  • ANC ≥ 1500/mm3 without colony stimulating factor support;
  • Platelets ≥ 100,000/mm3;
  • Hemoglobin ≥ 9 g/dL;
  • Bilirubin ≤ 1.5 x ULN. For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL;
  • Serum albumin ≥ 2.8 g/dl;
  • 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;
  • ALT and AST ≤ 3.0 x ULN;
  • Lipase < 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis;
  • UPCR ≤ 1;
  • Serum phosphorus, calcium, magnesium and potassium ≥ LLN.
  • The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  • 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).

Who cannot join

  • 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;
  • Prior treatment with cabozantinib;
  • 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;
  • 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;
  • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment;
  • 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;
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  • 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;
  • 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. ;
  • The subject has experienced any of the following:
  • clinically-significant GI bleeding within 6 months before the first dose of study treatment;
  • hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment;
  • any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.
  • The subject has radiographic evidence of cavitating pulmonary lesion(s);
  • The subject has tumor invading or encasing any major blood vessels;
  • 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;
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • 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).
  • 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;
  • 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;
  • QTcF > 500 msec within 1 month before the first dose of study treatment:
  • 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.
  • Pregnant or lactating females;
  • Inability to swallow intact tablets;
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations;
  • 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;

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Universtiy of Colorado Denver

    Aurora, Colorado, 80045

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Lone Tree Health Center

    Lone Tree, Colorado, 80124

  • Kenneth Norris Jr. Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Swedish Medical Center

    Seattle, Washington, 98122

  • University of Arizona

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: An Open-Label, Single-Arm, Two-Stage Phase II Study Investigating Cabozantinib in Patients With Refractory Metastatic Colorectal Cancer

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

Read the 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.

Being tested
Oral Tablet: Cabozantinib
Keywords
Cabozantinib, Progression Free Survival, Metastatic Colorectal Cancer, Tumor
Medical subject headings
Colorectal Neoplasms, Neoplasms

What participants receive

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

  • Oral Tablet: CabozantinibDrug

    Also called Cometriq, Cabometyx

    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.

Study groups in NCT03542877
Study groupRoleWhat they receive
Oral CabozantinibExperimentalPatients 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.
Receives: Drug: Oral Tablet: Cabozantinib

What is being measured

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

  1. 12-Week Progression Free Survival

    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.

    Measured: 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.

Secondary outcomes (9)

  1. 12-Week Progression-Free Survival by RAS Mutation Status

    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.

    Measured: 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.

  2. 12-Week Progression-Free Survival by PIK3CA Mutation Status

    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.

    Measured: 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.

  3. Progression-Free Survival (PFS)

    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.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  4. Progression-Free Survival (PFS) by RAS Mutation Status

    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.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  5. Progression-Free Survival (PFS) by PIK3CA Mutation Status

    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.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  6. Response Rate in Patients With CRC Treated With Cabozantinib

    *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.

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  7. Overall Survival (OS) in Patients With CRC Treated With Cabozantinib

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

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  8. Overall Survival (OS) by RAS Mutation Status

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

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

  9. Overall Survival (OS) by PIK3CA Mutation Status

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

    Measured: Study start date to study end date, or death, whichever comes first, up to 24 months

Timeline

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

  1. First posted31 May 2018
  2. Study start1 Jun 2018
  3. Primary completion19 Oct 2020
  4. Study completion7 Mar 2022

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03542877
Sponsor's protocol ID
18-0021.cc
Status last verified
Jun 2022
First submitted
23 Apr 2018
Last updated
15 Jul 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oral Tablet: Cabozantinib in people with Colorectal Cancer, run by Academic Thoracic Oncology Medical Investigators Consortium at 10 sites 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 22 inclusion and 30 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: finished, as of the sponsor's last update on 15 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 2 Jun 2022). 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?

12-Week Progression Free Survival (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.). 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 NCT03542877.

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 15 Jul 2022.

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Clinical Trial NCT03542877 | AzTrials