Cabozantinib and Erlotinib for Patients With EGFR and c-Met Co-expressing Metastatic Pancreatic Adenocarcinoma

NCT03213626 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IUSCC-0597
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, single arm, phase II trial. Safety will be monitored on an ongoing basis. Laboratory testing (chemistry, hematology tests) will be performed every 2 weeks for the first 8 weeks followed by assessments every 4 weeks. Other safety evaluations including EKGs, urinalysis, coagulation and thyroid function studies will be performed at regular intervals. Adverse event seriousness, severity grade, and relationship to study treatment will be assessed by the investigator. Severity grade will be defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Tumors will be assessed by contrast enhanced CT or MRI every 8 weeks. Pre-treatment tissue will be obtained via CT-guided FNA biopsy or collected during resection. However, archival tissue will also be requested, when available and if adequate for testing. Post-treatment tissue will be obtained on Day 15 (i.e., Week 3/Day 1) via CT-guided FNA biopsy. All tumor tissue from eligible patients will be utilized for the correlative studies which are outlined in this trial. Each subject's course will consist of three periods:

• A Pre-Treatment Period in which subjects are consented and undergo screening assessments to be qualified for the study;
• A Treatment Period in which subjects receive study treatment and undergo study assessments. Patients who meet the eligibility criteria will be treated with cabozantinib orally at 40 mg daily and erlotinib orally at 100 mg daily without breaks;
• A Post-Treatment Period in which subjects no longer receive study treatment but undergo follow-up study assessments and contacts.

Conditions

Pancreatic Adenocarcinoma Metastatic

Outcome Measures

Primary Outcomes (1)

• Objective (Radiographic) Response

  Percent of patients with Objective response and the Binomial Exact 95% confidence interval. Objective response is defined as having a best response of Complete Response (defined as disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10mm) or Partial Response (defined as at least a 30% decrease in the sum of diameters of target lesions from the baseline sum diameters) by RECIST v1.1 criteria.

  8 weeks

Secondary Outcomes (4)

• Disease Control Rate

  8 weeks

• Progression Free Survival

  2 years

• Overall Survival

  2 years

• Treatment Related Adverse Events Grade 3 or Above

  Up to 5 months

Study Arms (1)

Cabozantinib + erlotinib

EXPERIMENTAL

Drug: Cabozantinib 40 MG; Drug: Erlotinib 100Mg Tab

Interventions

Cabozantinib 40 MG DRUG

To be taken orally once daily

Cabozantinib + erlotinib

Erlotinib 100Mg Tab DRUG

To be taken orally once daily

Cabozantinib + erlotinib

Eligibility Criteria

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

You may qualify if:

• A subject must fully meet all of the following criteria to be eligible for the study:
• The subject has a biopsy-proven diagnosis of adenocarcinoma of the pancreas (or recurrence of previously resected disease) with metastatic disease that is measurable per RECIST 1.1;
• The subject must have tumor that is amenable to fine needle biopsy via computerized tomography (CT) guided approach OR an archived tissue sample such as a prior surgical sample or biopsy sample that is adequate for testing;
• The subject must have EGFR and c-Met overexpressed in tumor as determined by immunohistochemistry (IHC) test score of 2+ for both markers;
• The subject has demonstrated radiographic progression after front-line treatment for locally advanced or metastatic disease (prior adjuvant therapy allowed if ≥ 6 months elapsed between end of adjuvant therapy and metastatic relapse);
• 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;
• The subject has recovery to baseline or ≤ Grade 1 CTCAE v.4.03 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy;
• The subject has organ and marrow function and laboratory values as follows within 7 days before the first dose of study treatment:
• The ANC ≥ 1500/mm3 without colony stimulating factor support;
• Platelets ≥ 100,000/mm3;
• Hemoglobin ≥ 9 g/dL;
• Bilirubin ≤ 1.5 x the ULN. For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL;
• AST/ALT ≤ 3 x the ULN;
• Serum albumin ≥ 2.8 g/dl;

You may not qualify if:

• A subject who meets any of the following criteria is ineligible for the study:
• The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment;
• Prior treatment with cabozantinib or erlotinib;
• 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;
• 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;
• Concomitant anticoagulation at therapeutic doses with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel); Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose LMWH are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• 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; and
• clinically confirmed history of interstitial lung disease (ILD).
• The subject has radiographic evidence of cavitating pulmonary lesion(s);
• The subject has tumor invading or encasing any major blood vessels;

Sponsors & Collaborators

• Patrick Joseph Loehrer Sr.: lead
• Exelixis: collaborator

Study Sites (2)

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Interventions

cabozantinib; Erlotinib Hydrochloride

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Patrick Loehrer
• Organization: IndianaU

ploehrer@iu.edu

(317) 278-7418

Study Officials

• Bert H. O'Neil, MD

  Indiana University School of Medicine

  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: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Dean for Cancer Research Director, Indiana University Melvin and Bren Simon Cancer Center

Study Record Dates

• First Submitted: July 7, 2017
• First Posted: July 11, 2017
• Study Start: October 13, 2017
• Primary Completion: April 15, 2019
• Study Completion: November 18, 2019
• Last Updated: August 27, 2020
• Results First Posted: August 27, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)