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Study of Ixazomib and Erlotinib in Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02942095
Recruitment Status : Active, not recruiting
First Posted : October 21, 2016
Last Update Posted : September 9, 2019
Sponsor:
Collaborator:
Millennium: The Takeda Oncology Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of the combination of ixazomib and erlotinib that can be given to patients with advanced solid tumors. The safety of these drugs will also be studied.

This is an investigational study. Erlotinib is FDA approved and commercially available to treat non-small cell lung cancer, but its use in advanced solid cancer is considered investigational. Ixazomib is FDA approved. The study doctor can explain how the study drugs are designed to work.

Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Ixazomib Drug: Erlotinib Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Ixazomib and Erlotinib in Advanced Solid Tumor Patients
Actual Study Start Date : March 6, 2017
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation Group - Ixazomib + Erlotinib

Dose Escalation Phase: Participants take Ixazomib capsules by mouth on Days 1, 8, and 15 of each 28 day cycle starting with Dose Level 1.

Participants take Erlotinib tablets by mouth on Days 1 - 28 of each 28 day cycle.

Drug: Ixazomib

Dose Escalation Phase Starting Dose: Ixazomib 3.0 mg on Days 1, 8, and 15 of a 28-day cycle.

Dose Expansion Phase: Maximum tolerated dose from Dose Escalation Phase

Other Name: MLN9708

Drug: Erlotinib
Dose Escalation and Dose Expansion Phase: Erlotinib 150 mg by mouth on Days 1 - 28 of a 29 day cycle.
Other Names:
  • Erlotinib Hydrochloride
  • OSI-774
  • CP358774
  • Tarceva

Experimental: Dose Expansion Group - Non Small Cell Lung Cancer

Dose Expansion Phase : Participants take Ixazomib capsules by mouth on Days 1, 8, and 15 of each 28 day cycle at the maximum tolerated dose from Dose Escalation Phase.

Participants take Erlotinib tablets by mouth on Days 1 - 28 of each 28 day cycle.

Drug: Ixazomib

Dose Escalation Phase Starting Dose: Ixazomib 3.0 mg on Days 1, 8, and 15 of a 28-day cycle.

Dose Expansion Phase: Maximum tolerated dose from Dose Escalation Phase

Other Name: MLN9708

Drug: Erlotinib
Dose Escalation and Dose Expansion Phase: Erlotinib 150 mg by mouth on Days 1 - 28 of a 29 day cycle.
Other Names:
  • Erlotinib Hydrochloride
  • OSI-774
  • CP358774
  • Tarceva

Experimental: Dose Expansion Group - Pancreatic Ductal Adenocarcinoma

Dose Expansion Phase : Participants take Ixazomib capsules by mouth on Days 1, 8, and 15 of each 28 day cycle at the maximum tolerated dose from Dose Escalation Phase.

Participants take Erlotinib tablets by mouth on Days 1 - 28 of each 28 day cycle.

Drug: Ixazomib

Dose Escalation Phase Starting Dose: Ixazomib 3.0 mg on Days 1, 8, and 15 of a 28-day cycle.

Dose Expansion Phase: Maximum tolerated dose from Dose Escalation Phase

Other Name: MLN9708

Drug: Erlotinib
Dose Escalation and Dose Expansion Phase: Erlotinib 150 mg by mouth on Days 1 - 28 of a 29 day cycle.
Other Names:
  • Erlotinib Hydrochloride
  • OSI-774
  • CP358774
  • Tarceva




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Ixazomib and Erlotinib in Advanced Cancer Participants [ Time Frame: 28 days ]

    MTD defined by dose limiting toxicities (DLTs) that occur during the first cycle.

    Dose limiting toxicity (DLT) defined as

    1. Any Grade 3 or 4 non-hematologic toxicity as defined in the NCI CTCAE.
    2. Any Grade 4 hematologic toxicity lasting two weeks or longer (as defined by the NCI-CTCAE), despite supportive care.
    3. Grade 4 nausea, vomiting or diarrhea > 5 days despite maximum anti-nausea regimens.


Secondary Outcome Measures :
  1. Tumor Response of Ixazomib and Erlotinib in Participants with Non Small Cell Lung Cancer [ Time Frame: 8 weeks ]
    Tumor response of this combination per RECIST version 1.1.

  2. Tumor Response of Ixazomib and Erlotinib in Participants with Pancreatic Ductal Adenocarcinoma [ Time Frame: 8 weeks ]
    Tumor response of this combination per RECIST version 1.1.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with advanced or metastatic cancer that is refractory to standard therapy or that has relapsed after standard therapy or has no standard therapy that increases survival by at least three months.
  2. All prior treatment- related toxicities must be CTCAE (Version 4.0) less than or equal to Grade 2 (except alopecia) at the time of screening however clinically relevant AEs that will impact on the ADE of the study drugs or safety of the subject must have resolved to Grade 1 or better.
  3. Adequate baseline organ function defined as following: Absolute neutrophil count greater than or equal to 1.5 x 109 cells/L, hemoglobin greater than or equal to 8.0 g/dL, platelets greater than or equal to 75 x 109/L, creatinine less than or equal to 1.5 X upper limit of normal (ULN) with calculated creatinine clearance greater than 30 ml/min, total bilirubin less than or equal to 1.5 X ULN, AST(SGOT) and/or ALT(SGPT) less than or equal to 3 XULN.
  4. 18 years of age or older.
  5. Life expectancy of at least 3 months in the opinion of investigator.
  6. Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  7. Measurable disease as defined by RECIST criteria (Version 1.1).
  8. Patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  9. Having archival paraffin tissue is ideal for the correlative study but it is not mandatory.
  10. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  11. Female patients who: Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods]), And latex or non-latex condom with or without a spermicidal agent, Diaphragm with spermicide; Cervical cap with a spermicide; Sponge with a spermicide
  12. Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: a) Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR b) Latex or non-latex condom with or without a spermicidal agent, Diaphragm with spermicide; Cervical cap with a spermicide; Sponge with a spermicide.
  13. Inclusion Criteria for dose expansion cohort: Non-small cell lung cancer: 1) We will enroll non-small cell lung cancer patients with documented EGFR mutation who failed treatment with anti-EGFR therapy (e.g. erlotinib or afatinib) and tested negative for EGFR T790M mutation. We will allow patients with positive EGFR T790M mutation if they have progressed on third generation anti-EGFR therapy (e.g. CO-1686 or AZD9291) or medically not suitable/candidate for the third generation anti-EGFR therapy. Failure from anti-EGFR therapy will be defined as progressive disease by RECIST (Version 1.1) after at least two months of therapy. We plan to enroll up to 9 patients in this cohort.
  14. Pancreatic ductal adenocarcinoma: 1) Pancreatic ductal adenocarcinoma patient with KRAS point mutation at codon G12 or G13. Since KRAS mutation is present in more than 90% of pancreatic cancer with 98% of the mutation found at codon 12, we expect majority of patients with pancreatic ductal adenocarcinoma will be eligible for the study. We plan to enroll up to 9 patients in this cohort. In addition to the above inclusion criteria, first 5 patients from both non-small cell lung cancer and pancreatic ductal adenocarcinoma patients will need to agree to mandatory pre- and post-treatment tumor biopsies.

Exclusion Criteria:

  1. Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator.
  2. Radiotherapy completed within 2 weeks prior to treatment initiation. Radiotherapy completed >2 weeks prior to treatment initiation is allowed if all procedure-related toxicities resolved per inclusion #2.
  3. Patient who were receiving prior therapy will require wash out period of either more than 2 weeks or more than 5 half-lives whichever shorter.
  4. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
  5. Current use of a prohibited medication.
  6. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. If these were treated and clinically stable for 4 weeks, patient can be considered for the trial.
  7. Patient who is on strong inducer/inhibitor of CYP3A needs to be off the medication prior to treatment initiation unless it is medically necessary for the patient.
  8. Female patients who are lactating or have a positive serum pregnancy test suggestive of pregnancy and not as a tumor marker during the screening period. If pregnancy is tested positive, treating physician will further investigate if the patient is pregnant or not. Treating physician may consider repeating the serum beta-hCG at next follow up visit or refer patient to OB/GYN for further evaluation.
  9. Major surgery within 14 days before enrollment.
  10. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
  11. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
  12. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
  13. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  14. Patient has greater than or equal than Grade 2 peripheral neuropathy, or Grade 1 with pain on clinical examination during the screening period.
  15. Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02942095


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Millennium: The Takeda Oncology Company
Investigators
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Principal Investigator: David S. Hong, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02942095     History of Changes
Other Study ID Numbers: 2015-0688
NCI-2016-01931 ( Registry Identifier: NCI CTRP )
First Posted: October 21, 2016    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Advanced Solid Tumors
Metastatic cancer
Ixazomib
MLN9708
Erlotinib
Erlotinib hydrochloride
OSI-774
CP358774
Tarceva
Additional relevant MeSH terms:
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Neoplasms
Erlotinib Hydrochloride
Ixazomib
Glycine
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs