Investigating Cabozantinib in Patients With Refractory Metastatic Colorectal Cancer

NCT03542877 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-0021.cc
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

Colorectal Cancer

Keywords

Cabozantinib; Progression Free Survival; Metastatic Colorectal Cancer; Tumor

Outcome Measures

Primary Outcomes (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.

  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)

• 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.

• 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.

• Progression-Free Survival (PFS)

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

• Progression-Free Survival (PFS) by RAS Mutation Status

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

• Progression-Free Survival (PFS) by PIK3CA Mutation Status

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

Study Arms (1)

Oral Cabozantinib

EXPERIMENTAL

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

Interventions

Oral Tablet: Cabozantinib DRUG

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.

Also known as: Cometriq, Cabometyx

Oral Cabozantinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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);

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

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

Study Sites (10)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Kenneth Norris Jr. Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Universtiy of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Lone Tree Health Center

Lone Tree, Colorado, 80124, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Jefferson Abington Hospital

Abington, Pennsylvania, 19001, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Dr. Wells Messersmith
• Organization: University of Colorado

wells.messersmith@cuanschutz.edu

303-724-0747

Study Officials

• Wells Messersmith, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 31, 2018
• Study Start: June 1, 2018
• Primary Completion: October 19, 2020
• Study Completion: March 7, 2022
• Last Updated: July 15, 2022
• Results First Posted: June 2, 2022

Record last verified: 2022-06

Locations

US (10)