Breast CancerPhase 1D-1MTNCT00739609
IDO Inhibitor Study for Relapsed or Refractory Solid Tumors
A Phase 1 study testing 1-methyl-D-tryptophan in people with Breast Cancer and Lung Cancer, run by NewLink Genetics Corporation at 1 site in United States.
Trial summary
This study provides an early evaluation of an entirely new class of small molecule agents directed at disruption or elimination of tumor tolerance, a phenomenon now demonstrated to be involved in the growth of many solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Lung Cancer, Melanoma
- What is being tested?
- 1-methyl-D-tryptophan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Oct 2012
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A histological or cytological diagnosis of recurrent or refractory solid tumor malignancy. The patient's pathology must be reviewed and confirmed prior to enrollment (outside reviews acceptable). If no standard therapy exists for disease or subject refused standard therapy, subject would be considered eligible for enrollment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- Hemoglobin ≥ 9.0 gm/dL, absolute neutrophil count (ANC) ≥1200/mm3, platelets ≥100,000/mm3, absolute lymphocyte count ≥800/mm3.
- Hepatic: serum total bilirubin ≤ 1.5 x ULN mg/dL, ALT (SGPT) and AST (SGOT) ≤2.5 x upper limit of normal (ULN).
- Renal: serum creatinine (sCr) ≤1.5 x ULN, or creatinine clearance (Ccr) ≥50 mL/min (approximation by Cockcroft and Gault accepted)
- Life expectancy of greater than 4 months.
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- Measurable or non-measurable disease
- Normal EKG including benign variants or abnormalities associated with any condition currently responding to appropriate care (e.g., controlled hypertension with minimal or moderate LVH, controlled AF).
- Prior therapy may include any number of chemotherapy, immunotherapy, and/or radiation therapy regimens. Major surgery or systemic chemotherapy must have been completed at least 4 weeks prior to enrollment and residual toxicities from that therapy must be Grade 1 or lower at the time of enrollment with the exception of hemoglobin and absolute granulocyte count. Localized radiation therapy must have been completed at least 2 weeks prior to enrollment and residual toxicities must be Grade 1 or lower at the time of enrollment.
- Patients must have the ability to understand the study, its inherent risks, side effects and potential benefits and be able to give written informed consent to participate.
- Male and female subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental drug, and for one month after the last dose of drug.
- Patients must be at least 18 years of age
Who cannot join
- Active CNS metastases or carcinomatous meningitis. Patients with CNS metastases must be at least 3 months status post of prior therapy to the brain and be off all steroids without progressing CNS disease.
- Pregnant or nursing women due to the unknown effects of study drug on the developing fetus or newborn infant.
- History of gastrointestinal disease causing malabsorption or obstruction such as but not limited to Crohn's disease, celiac sprue, tropical sprue, bacterial overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions, achalasia, bowel obstruction, or extensive small bowel resection.
- History of organ transplant.
- Subjects with autoimmune disease, either active or by history (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis (RA), scleroderma, dermatomyositis, etc.).
- Subjects receiving immunosuppressive therapy including systemic corticosteroid therapy and/other immunosuppressive therapy (methotrexate, cyclosporine, FK-506, rapamycin) for any reason. Subjects receiving inhaled or topical corticosteroids are eligible.
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- Significant or uncontrolled cardiovascular disease to include: uncontrolled hypertension (blood pressure must be ≤ 150/90 mmHg at the time of enrollment on a stable antihypertensive regimen); New York Heart Association grade II or greater congestive heart failure (CHF); grade II or greater peripheral vascular disease; significant ventricular arrhythmias requiring medication; and myocardial infarction or unstable angina < six months prior to enrollment.
- Active uncontrolled infection requiring antibiotics within 1-week prior to study, including unexplained fever (temp > 38.1°C or >100.6°F).
- Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc.).
- No supplements containing L-trytophan or derivatives thereof are allowed to be taken while on study.
- Patients with positive serology for HIV, Hepatitis B or C, and patients with other acquired/inherited immunodeficiencies are ineligible due to the possibility of affecting the response to D-1MT and the higher risk of active opportunistic infections.
- Patients with more than one active malignancy at the time of enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of Indoximod [1-methyl-D-tryptophan (D-1MT)] in Patients With Relapsed or Refractory Solid Tumors
This study provides an early evaluation of an entirely new class of small molecule agents directed at disruption or elimination of tumor tolerance, a phenomenon now demonstrated to be involved in the growth of many solid tumors.
Read the detailed description
This protocol provides an early evaluation of an entirely new class of small molecule agents directed at disruption or elimination of tumor tolerance, a phenomenon now demonstrated to be involved in the growth of many solid tumors. D-1MT, or any other substance targeting this enzymatic pathway indoleamine-(2,3)-dioxygenase (IDO), has not been used previously in humans. Although pre-clinical toxicology in rats and dogs shows an extremely encouraging toxicity profile, the study needs to carefully evaluate the toxicities and pharmacokinetics to provide the basis for assigning a safe and biologically effective dosing regimen for later trials determining its contribution to tumor responses in phase II and III clinical trials.
- Conditions
- Breast Cancer, Lung Cancer, Melanoma, Pancreatic Cancer, Solid Tumors
- Being tested
- 1-methyl-D-tryptophan
- Medical subject headings
- Breast Neoplasms, Lung Neoplasms, Melanoma, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1-methyl-D-tryptophanDrug
Also called D-1MT, NSC-721782, 1-MT
D-1MT will be administered in escalating doses. Initial dosing will be 200 mg by mouth daily with escalation planned to 2000 mg by mouth daily and potentially higher doses in subsequent cohorts if tolerated and pharmacokinetic and biologic data support further dose escalation.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: 1-methyl-D-tryptophan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety and efficacy of administration of D-1MT into patients with recurrent or refractory solid tumors. Establish the toxicities of D-1MT and define any dose limiting toxicities if they occur below the maximum doses.
Measured: 6 months
Secondary outcomes (1)
Preliminarily characterize effects of D-1MT on serum kynurenine levels as a biomarker for systemic IDO activity.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionOct 2012
- Study completionOct 2012
Why it stopped: Lack of enrollment.
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 Breast CancerStudies of the same condition, open and under way.
- 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- NewLink Genetics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Charles J. Link, M.D., Study chair, NewLink Genetics Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00739609
- Sponsor's protocol ID
- NLG2100
- Acronym
- D-1MT
- Status last verified
- May 2020
- First submitted
- 20 Aug 2008
- Last updated
- 28 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ino K. Indoleamine 2,3-dioxygenase and immune tolerance in ovarian cancer. Curr Opin Obstet Gynecol. 2011 Feb;23(1):13-8. doi: 10.1097/GCO.0b013e3283409c79.
PubMed 20930628
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Indoximod [1-methyl-D-tryptophan (D-1MT)] in Patients With Relapsed or Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT00739609
- Acronym / sponsor ID
- D-1MT / NLG2100
- Conditions
- Breast Cancer, Lung Cancer, Melanoma, Pancreatic Cancer, Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- NewLink Genetics CorporationIndustry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 22 Aug 2008 (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 study provides an early evaluation of an entirely new class of small molecule agents directed at disruption or elimination of tumor tolerance, a phenomenon now demonstrated to be involved in the growth of many solid tumors.
Detailed description
This protocol provides an early evaluation of an entirely new class of small molecule agents directed at disruption or elimination of tumor tolerance, a phenomenon now demonstrated to be involved in the growth of many solid tumors. D-1MT, or any other substance targeting this enzymatic pathway indoleamine-(2,3)-dioxygenase (IDO), has not been used previously in humans. Although pre-clinical toxicology in rats and dogs shows an extremely encouraging toxicity profile, the study needs to carefully evaluate the toxicities and pharmacokinetics to provide the basis for assigning a safe and biologically effective dosing regimen for later trials determining its contribution to tumor responses in phase II and III clinical trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: 1-methyl-D-tryptophan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- A histological or cytological diagnosis of recurrent or refractory solid tumor malignancy. The patient's pathology must be reviewed and confirmed prior to enrollment (outside reviews acceptable). If no standard therapy exists for disease or subject refused standard therapy, subject would be considered eligible for enrollment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- Hemoglobin ≥ 9.0 gm/dL, absolute neutrophil count (ANC) ≥1200/mm3, platelets ≥100,000/mm3, absolute lymphocyte count ≥800/mm3.
- Hepatic: serum total bilirubin ≤ 1.5 x ULN mg/dL, ALT (SGPT) and AST (SGOT) ≤2.5 x upper limit of normal (ULN).
- Renal: serum creatinine (sCr) ≤1.5 x ULN, or creatinine clearance (Ccr) ≥50 mL/min (approximation by Cockcroft and Gault accepted)
Key exclusion criteria (12 listed)
- Active CNS metastases or carcinomatous meningitis. Patients with CNS metastases must be at least 3 months status post of prior therapy to the brain and be off all steroids without progressing CNS disease.
- Pregnant or nursing women due to the unknown effects of study drug on the developing fetus or newborn infant.
- History of gastrointestinal disease causing malabsorption or obstruction such as but not limited to Crohn's disease, celiac sprue, tropical sprue, bacterial overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions, achalasia, bowel obstruction, or extensive small bowel resection.
- History of organ transplant.
- Subjects with autoimmune disease, either active or by history (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis (RA), scleroderma, dermatomyositis, etc.).
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 |
|---|---|---|
| 1-methyl-D-tryptophanAlso: D-1MT, NSC-721782, 1-MTD-1MT will be administered in escalating doses. Initial dosing will be 200 mg by mouth daily with escalation planned to 2000 mg by mouth daily and potentially higher doses in subsequent cohorts if tolerated and pharmacokinetic and biologic data support further dose escalation. | Drug | 1 |
Primary outcome
Determine the safety and efficacy of administration of D-1MT into patients with recurrent or refractory solid tumors. Establish the toxicities of D-1MT and define any dose limiting toxicities if they occur below the maximum doses.
Time frame: 6 months
1 secondary outcome
Preliminarily characterize effects of D-1MT on serum kynurenine levels as a biomarker for systemic IDO activity.
Time frame: 3 months
Results and safety
The study was stopped early (reason given: Lack of enrollment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2020.
- Derived from this study: PubMed 20930628Ino K. Indoleamine 2,3-dioxygenase and immune tolerance in ovarian cancer. Curr Opin Obstet Gynecol. 2011 Feb;23(1):13-8. doi: 10.1097/GCO.0b013e3283409c79.
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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.
Charles J. Link, M.D. study chair
NewLink Genetics Corporation
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 1-methyl-D-tryptophan in people with Breast Cancer and Lung Cancer, run by NewLink Genetics Corporation 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 12 inclusion and 12 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 28 May 2020. 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 was stopped early (reason given: Lack of enrollment.). Results are not available in the source record.
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?
Determine the safety and efficacy of administration of D-1MT into patients with recurrent or refractory solid tumors. Establish the toxicities of D-1MT and define any dose limiting toxicities if they occur below the maximum doses. (time frame: 6 months). 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 NCT00739609, 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 28 May 2020.