Study of Ixazomib and Erlotinib in Solid Tumors

NCT02942095 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2015-0688NCI-2016-01931
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors

Keywords

Advanced Solid Tumors; Metastatic cancer; Ixazomib; MLN9708; Erlotinib; Erlotinib hydrochloride; OSI-774; CP358774; Tarceva

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Ixazomib and Erlotinib in Advanced Cancer Participants

  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.

  28 days

Secondary Outcomes (2)

• Tumor Response of Ixazomib and Erlotinib in Participants with Non Small Cell Lung Cancer

  8 weeks

• Tumor Response of Ixazomib and Erlotinib in Participants with Pancreatic Ductal Adenocarcinoma

  8 weeks

Study Arms (3)

Dose Escalation Group - Ixazomib + Erlotinib

EXPERIMENTAL

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; Drug: Erlotinib

Dose Expansion Group - Non Small Cell Lung Cancer

EXPERIMENTAL

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; Drug: Erlotinib

Dose Expansion Group - Pancreatic Ductal Adenocarcinoma

EXPERIMENTAL

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; Drug: Erlotinib

Interventions

Ixazomib DRUG

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

Also known as: MLN9708

Dose Escalation Group - Ixazomib + Erlotinib; Dose Expansion Group - Non Small Cell Lung Cancer; Dose Expansion Group - Pancreatic Ductal Adenocarcinoma

Erlotinib DRUG

Dose Escalation and Dose Expansion Phase: Erlotinib 150 mg by mouth on Days 1 - 28 of a 29 day cycle.

Also known as: Erlotinib Hydrochloride, OSI-774, CP358774, Tarceva

Dose Escalation Group - Ixazomib + Erlotinib; Dose Expansion Group - Non Small Cell Lung Cancer; Dose Expansion Group - Pancreatic Ductal Adenocarcinoma

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.
• years of age or older.
• Life expectancy of at least 3 months in the opinion of investigator.
• 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.
• Measurable disease as defined by RECIST criteria (Version 1.1).
• Patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Having archival paraffin tissue is ideal for the correlative study but it is not mandatory.
• 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.
• 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
• 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.

You may not qualify if:

• 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.
• 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.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
• Current use of a prohibited medication.
• 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.
• 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.
• 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.
• Major surgery within 14 days before enrollment.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
• 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.
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
• 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.
• Patient has greater than or equal than Grade 2 peripheral neuropathy, or Grade 1 with pain on clinical examination during the screening period.
• Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Millennium: The Takeda Oncology Company: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

ixazomib; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• David S. Hong, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2016
• First Posted: October 21, 2016
• Study Start: March 6, 2017
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022
• Last Updated: April 18, 2023

Record last verified: 2023-04

Locations

US (1)