Advanced Malignant Solid NeoplasmPhase 1NCT01738139
Ipilimumab and Imatinib Mesylate in Advanced Cancer
A Phase 1 study testing Imatinib Mesylate and Ipilimumab in people with Advanced Malignant Solid Neoplasm and C-KIT Tyrosine Kinase Protein Overexpression, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of ipilimumab and imatinib mesylate in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Advanced Malignant Solid Neoplasm, C-KIT Tyrosine Kinase Protein Overexpression, Clinical Stage IV Cutaneous Melanoma AJCC v8
- What is being tested?
- Imatinib Mesylate and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Feb 2013to 13 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- For dose escalation study, patients must have histological confirmation of solid tumors that is metastatic or unresectable. For expansion cohorts, patients must have metastatic or unresectable gastrointestinal stromal tumor (GIST), melanoma, or uncategorized tumors with tumor biopsies that are positive for c-KIT mutations by polymerase chain reaction (PCR) or immunohistochemistry (IHC). For patients enrolled in the melanoma expansion cohort, only select KIT mutations will be eligible. Patients with mutations in exon 13 V654X, 14 T6701, 17 D816X and all exon 18 mutations will not be eligible for enrollment.
- Patients who have completed previous therapies 4-weeks prior to (or within 5 drug half lives) enrollment on study. Radiation therapy wash out period will be 2 weeks. This includes an exception of patients with metastatic GIST tumors who are taking maintenance imatinib mesylate therapy. These patients are allowed to remain on imatinib mesylate therapy up to enrollment in this study.
- Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%).
- Leukocytes > 3,000/mcL
- Absolute neutrophil count > 1,500/mcL
- Platelets > 100,000/mcL
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- Total bilirubin < or = 2.0 mg/dL. (Does NOT apply to patients with Gilbert's syndrome)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal (patients with liver involvement will be allowed < or = 5.0 X institutional upper normal limit)
- Serum creatinine < 2.0 mg/dL
- Patients MUST have recovered from all treatment related toxicities to grade 1 National Center Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version [v] 4.0) in severity.
- Patients must be willing and able to review, understand, and provide written consent before starting therapy.
- Patients with histologically proven intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma will be eligible. Patients must have shown unequivocal radiographic evidence for tumor progression by magnetic resonance imaging (MRI) scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required.
- Patients in the expansion cohort must also agree to participate in the biomarker study. However, patients in the melanoma KIT positive mutant subgroup, patients must agree to participate in the biomarker study and biopsies.
- Patients must be willing to stay within 2 hours drive of MD Anderson Cancer Center whilst receiving Ipilimumab therapy. Patient must also agree to present to MD Anderson emergency center while on Ipilimumab therapy.
Who cannot join
- Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus or autoimmune vasculitis [e.g., Wegener's granulomatosis] are excluded from this study.
- History of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs): e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- Any non-oncology live vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).
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- Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids (when used in the management of cancers other than intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma, or when used to treat non-cancer-related illnesses).
- Patients who do not agree to practice appropriate birth control methods while on therapy.
- Pregnant women are excluded from this study. Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial of Ipilimumab (Immunotherapy) and Imatinib Mesylate (c-Kit Inhibitor) in Patients With Advanced Malignancies
This phase I trial studies the side effects and best dose of ipilimumab and imatinib mesylate in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ipilimumab and imatinib mesylate may work better in treating patients with solid tumors.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and toxicity profile of intravenous ipilimumab (Yervoy) administered in combination with oral imatinib mesylate (GLEEVEC) for patients with advanced malignancies that are refractory to standard therapy, relapsed after standard therapy, or have no available standard therapy.
II. To determine the maximum toxic dose (MTD) and dose limiting toxicities (DLT) of ipilimumab and imatinib mesylate combination therapy.
SECONDARY OBJECTIVES:
- To determine antitumor activity of ipilimumab and imatinib mesylate combination therapy.
II. To determine antitumor activity of ipilimumab and imatinib mesylate combination therapy in KIT confirmed solid tumors.
III. To evaluate the potential predictive role of tumor-associated immune biomarkers for therapy effectiveness.
IV. To evaluate the potential predictive role of therapy associated toxicities with antitumor activity.
OUTLINE: This is a dose-escalation study.
Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1 and imatinib mesylated orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Conditions
- Advanced Malignant Solid Neoplasm, C-KIT Tyrosine Kinase Protein Overexpression, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Gastrointestinal Stromal Tumor, Metastatic Malignant Solid Neoplasm, Metastatic Melanoma
- Being tested
- Imatinib Mesylate, Ipilimumab
- Medical subject headings
- Gastrointestinal Stromal Tumors, Neoplasm Metastasis, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib MesylateDrug
Also called CGP 57148, CGP57148B, Gleevec, Glivec
Given PO
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ipilimumab, imatinib mesylate) | Experimental | Patients receive ipilimumab IV over 90 minutes on day 1 and imatinib mesylate PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Imatinib Mesylate; Biological: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Measured: Up to 7 years
Maximum tolerated dose (MTD)
MTD determined as the highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort. DLT determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2012 (estimated)
- Study start19 Feb 2013
- Primary completion13 Dec 2022
- Study completion13 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- David S Hong, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01738139
- Sponsor's protocol ID
- 2012-0784
- Other IDs
- NCI-2018-01811, 2012-0784, P30CA016672
- Status last verified
- Mar 2024
- First submitted
- 28 Nov 2012
- Last updated
- 21 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Reilley MJ, Bailey A, Subbiah V, Janku F, Naing A, Falchook G, Karp D, Piha-Paul S, Tsimberidou A, Fu S, Lim J, Bean S, Bass A, Montez S, Vence L, Sharma P, Allison J, Meric-Bernstam F, Hong DS. Phase I clinical trial of combination imatinib and ipilimumab in patients with advanced malignancies. J Immunother Cancer. 2017 Apr 18;5:35. doi: 10.1186/s40425-017-0238-1. eCollection 2017.
PubMed 28428884
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Ipilimumab (Immunotherapy) and Imatinib Mesylate (c-Kit Inhibitor) in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT01738139
- Acronym / sponsor ID
- 2012-0784
- Conditions
- Advanced Malignant Solid Neoplasm, C-KIT Tyrosine Kinase Protein Overexpression, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Gastrointestinal Stromal Tumor, Metastatic Malignant Solid Neoplasm, Metastatic Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 19 Feb 2013 (actual)
- Primary completion
- 13 Dec 2022 (actual)
- Study completion
- 13 Dec 2023 (actual)
- First posted
- 30 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of ipilimumab and imatinib mesylate in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ipilimumab and imatinib mesylate may work better in treating patients with solid tumors.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and toxicity profile of intravenous ipilimumab (Yervoy) administered in combination with oral imatinib mesylate (GLEEVEC) for patients with advanced malignancies that are refractory to standard therapy, relapsed after standard therapy, or have no available standard therapy.
II. To determine the maximum toxic dose (MTD) and dose limiting toxicities (DLT) of ipilimumab and imatinib mesylate combination therapy.
SECONDARY OBJECTIVES:
- To determine antitumor activity of ipilimumab and imatinib mesylate combination therapy.
II. To determine antitumor activity of ipilimumab and imatinib mesylate combination therapy in KIT confirmed solid tumors.
III. To evaluate the potential predictive role of tumor-associated immune biomarkers for therapy effectiveness.
IV. To evaluate the potential predictive role of therapy associated toxicities with antitumor activity.
OUTLINE: This is a dose-escalation study.
Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1 and imatinib mesylated orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ipilimumab, imatinib mesylate) | Experimental | Drug: Imatinib Mesylate, Biological: IpilimumabPatients receive ipilimumab IV over 90 minutes on day 1 and imatinib mesylate PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- For dose escalation study, patients must have histological confirmation of solid tumors that is metastatic or unresectable. For expansion cohorts, patients must have metastatic or unresectable gastrointestinal stromal tumor (GIST), melanoma, or uncategorized tumors with tumor biopsies that are positive for c-KIT mutations by polymerase chain reaction (PCR) or immunohistochemistry (IHC). For patients enrolled in the melanoma expansion cohort, only select KIT mutations will be eligible. Patients with mutations in exon 13 V654X, 14 T6701, 17 D816X and all exon 18 mutations will not be eligible for enrollment.
- Patients who have completed previous therapies 4-weeks prior to (or within 5 drug half lives) enrollment on study. Radiation therapy wash out period will be 2 weeks. This includes an exception of patients with metastatic GIST tumors who are taking maintenance imatinib mesylate therapy. These patients are allowed to remain on imatinib mesylate therapy up to enrollment in this study.
- Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%).
- Leukocytes > 3,000/mcL
- Absolute neutrophil count > 1,500/mcL
Key exclusion criteria (9 listed)
- Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus or autoimmune vasculitis [e.g., Wegener's granulomatosis] are excluded from this study.
- History of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs): e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imatinib MesylateAlso: CGP 57148, CGP57148B, Gleevec, GlivecGiven PO | Drug | Treatment (ipilimumab, imatinib mesylate) |
| IpilimumabAlso: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4Given IV | Biological | Treatment (ipilimumab, imatinib mesylate) |
Primary outcome
Incidence of adverse events
Time frame: Up to 7 years
Maximum tolerated dose (MTD)
Time frame: 84 days
MTD determined as the highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort. DLT determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2024.
- Derived from this study: PubMed 28428884Reilley MJ, Bailey A, Subbiah V, Janku F, Naing A, Falchook G, Karp D, Piha-Paul S, Tsimberidou A, Fu S, Lim J, Bean S, Bass A, Montez S, Vence L, Sharma P, Allison J, Meric-Bernstam F, Hong DS. Phase I clinical trial of combination imatinib and ipilimumab in patients with advanced malignancies. J Immunother Cancer. 2017 Apr 18;5:35. doi: 10.1186/s40425-017-0238-1. eCollection 2017.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David S Hong principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imatinib Mesylate and Ipilimumab in people with Advanced Malignant Solid Neoplasm and C-KIT Tyrosine Kinase Protein Overexpression, run by M.D. Anderson Cancer Center at 1 site 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 14 inclusion and 9 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: finished, as of the sponsor's last update on 21 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of adverse events (time frame: Up to 7 years). The study lists 2 primary outcomes in all. 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 NCT01738139, which also lists 1 linked publication.
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 21 Mar 2024.