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Pancreatic Adenocarcinoma MetastaticPhase 2NCT03213626

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

A Phase 2 study testing Cabozantinib 40 MG and Erlotinib 100Mg Tab in people with Pancreatic Adenocarcinoma Metastatic, run by Patrick Joseph Loehrer Sr. at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Adenocarcinoma Metastatic
What is being tested?
Cabozantinib 40 MG and Erlotinib 100Mg Tab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
2 sitesUnited States
Study dates
13 Oct 2017to 18 Nov 2019
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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;
  • Serum creatinine ≤ 1.5 x the 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); ii. Female: Multiply above result by 0.85; h. UPCR ≤ 1; i. Serum phosphorus, calcium, magnesium and potassium ≥ LLN; j. Prothrombin time (PT)/INR or partial thromboplastin time (PTT) test < 1.3 x the ULN within 7 days before the first dose of study treatment;
  • The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document;
  • The subject has a life expectancy of 12 weeks or greater;
  • The subject is able to tolerate oral medications and no evidence of ongoing malabsorption;
  • All sexually active subjects of reproductive potential must agree to use both a medically accepted barrier method (e.g., male or female condom) and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s);
  • Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy or bilateral oophorectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.

Who cannot join

  • 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;
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  • 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;
  • The subject has evidence of 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. b. GI disorders particularly those associated with a high risk of perforation or fistula formation including: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., 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 first dose of study treatment Note: Complete healing of an intra-abdominal abscess must be confirmed prior first dose of study treatment 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;
  • Active smoker;
  • 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; malignancy felt by investigator to potentially affect subject survival or ability to evaluate disease response.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Indiana University Health Hospital

    Indianapolis, Indiana, 46202

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

Official title: A Phase II Trial of Cabozantinib and Erlotinib for Patients With EGFR and c-Met Co-expressing Metastatic Pancreatic Adenocarcinoma

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.

Read more

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.
Read the detailed description

Primary Objective The primary objective of this trial is to demonstrate a radiographic response rate of 15% or greater for the combination in a selected population.

Secondary Objectives

The secondary objectives of this trial are:

  • To estimate progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS); and
  • To assess safety and tolerability of this combination in the target patient population.

Correlative Objectives

The following tests will be performed on blood and tumor tissue samples collected during this trial to correlate with PFS and OS:

  • c-Met and EGFR mRNA by RT-qPCR
  • plasma HGF and soluble Met receptor
  • c-Met and EGFR phosphoprotein levels by IHC
  • KRAS mutation status
Being tested
Cabozantinib 40 MG, Erlotinib 100Mg Tab

What participants receive

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

  • Cabozantinib 40 MGDrug

    To be taken orally once daily

  • Erlotinib 100Mg TabDrug

    To be taken orally once daily

Study groups in NCT03213626
Study groupRoleWhat they receive
Cabozantinib + erlotinibExperimentalNot described
Receives: Drug: Cabozantinib 40 MG; Drug: Erlotinib 100Mg Tab

What is being measured

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

  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.

    Measured: 8 weeks

Secondary outcomes (4)

  1. Disease Control Rate

    Percent of patients achieving disease control and the Binomial Exact 95% confidence interval. Disease control 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) or Stable Disease for at least 4 months (defined by neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression) by RECIST v1.1 criteria.

    Measured: 8 weeks

  2. Progression Free Survival

    Duration of time from the start of treatment to time of documented progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients who do not progress or die will be censored on their last evaluation date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.

    Measured: 2 years

  3. Overall Survival

    Duration of time from the start of treatment to time of death due to any causes. Patients who do not die will be censored on their last known alive date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.

    Measured: 2 years

  4. Treatment Related Adverse Events Grade 3 or Above

    Number of unique patients who had a treatment related (possible, probable or definite) adverse events with grade >= 3.

    Measured: Up to 5 months

Timeline

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

  1. First posted11 Jul 2017
  2. Study start13 Oct 2017
  3. Primary completion15 Apr 2019
  4. Study completion18 Nov 2019

Why it stopped: There were no objective responses by patient 7.

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
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03213626
Sponsor's protocol ID
IUSCC-0597
Status last verified
Aug 2020
First submitted
7 Jul 2017
Last updated
27 Aug 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib 40 MG and Erlotinib 100Mg Tab in people with Pancreatic Adenocarcinoma Metastatic, run by Patrick Joseph Loehrer Sr. at 2 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: stopped early, as of the sponsor's last update on 27 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 27 Aug 2020). 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?

Objective (Radiographic) Response (time frame: 8 weeks). 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 NCT03213626.

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 27 Aug 2020.

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