AzTrials
AzTrials

MelanomaPhase 1/2NCT01590082

Doxycycline, Temozolomide and Ipilimumab in Melanoma

A Phase 1/2 study testing Doxycycline, Ipilimumab and Temozolomide in people with Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

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

Official record
Search all trials

Trial summary

The goal of this clinical research study is to find the highest tolerable dose of doxycycline that can be combined with temozolomide and ipilimumab in patients with advanced melanoma. The safety and level of effectiveness of the study drug combination will also be studied. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Doxycycline, Ipilimumab and Temozolomide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Nov 2012to Jul 2015
Phase
Phase 1/2
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

  • Patient must be age >/= 18 years.
  • Patients must have histologically or cytologically confirmed diagnosis of malignant (unresectable Stage III or Stage IV) melanoma, not amenable to resection with curative intent.
  • Patients must have metastatic melanoma which has >25% of melanoma cells stained positive for iNOS expression by chemiluminescence immunoassay analyzer (CLIA)-certified immunohistochemistry assay. However, in phase I portion of the study, the requirement of >25% of melanoma cells stained positive for iNOS expression does not apply.
  • Patients must be at least 21 days since surgery, radiation therapy and 6 weeks after immunotherapy with regimens including vaccines, interferon, IL-2, etc. and fully recovered from adverse effects of these therapies.
  • Patients must have evaluable disease for response.
  • There is no limit on the number of prior therapies for Phase I portion. For Phase II portion only, patients may have received less than or equal to 1 prior chemotherapy regimen for metastatic melanoma. There is no limit on prior immunotherapies or kinase inhibitors. Patients with prior ipilimumab therapy will be excluded during the phase II portion.
Show all 14Show fewer
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or1.
  • Patient must have adequate liver and renal function as documented by the following laboratory test results within 14 days prior to starting therapy: • total bilirubin less than or equal to 1.5 x upper limit of normal (ULN); • AST (SGOT) and ALT (SGPT) less than or equal to 2.5 X ULN or less than or equal to 5 X ULN if liver metastasis is present; • serum creatinine less than or equal to 1.2 X ULN
  • Patient must have adequate bone marrow function as documented by the following laboratory test results within 14 days prior to starting therapy: • platelets greater than 100,000/mm3; • absolute neutrophil count (ANC) greater than 1500/mm3; • hemoglobin greater than 9.0 g/dL;
  • Patient must have completed any prior chemotherapy, immunotherapy, radiation therapy, biological therapy, or other investigational cancer therapy at least 4 weeks prior to starting the study drug(s) and must have recovered from all acute side effects (to Common Toxicity Criteria for Adverse Effects (CTCAE) less than Grade 1) prior to initiation of the study drug(s). Patients who were receiving mitomycin C or nitrosoureas must be 6 weeks from the last administration of chemotherapy. For a prior BRAF inhibitor, the washout period is 7 days.
  • Patient (man or woman) must agree to practice effective contraception during the entire study period, unless documentation of infertility exists, and for at least 4 weeks after the last dose of the study drug(s).
  • Patient must be willing and able to sign the informed consent form.
  • Patient must be willing and able to self-administer orally and document all doses of doxycycline ingested.
  • Patients must be willing to have iNOS expression assay test done on disease easily amenable to biopsy or suitable tissue obtained within the last 3 months.

Who cannot join

  • Patients who have received doxycycline or other tetracycline-analogs within the 4 weeks prior to the first dose of the study drug.
  • For Phase II portion only, patients with a diagnosis of ocular melanoma will be excluded.
  • Patients with an inability to swallow tablets or capsules.
  • Patients with a symptomatic malabsorptive disorder (eg, Crohn's Disease) or removal of either the terminal ileus or more than 2/3 of the small intestine.
  • Patients with active brain metastases or primary central nervous system (CNS) malignancies; patients with previously treated brain metastasis may be included, provided that no requirement for steroids and no evidence of progression for greater than or equal to 8 weeks after a local brain treatment.
  • Patients with an active second malignancy.
Show all 9Show fewer
  • Patients who are pregnant or breastfeeding.
  • Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to:uncontrolled diabetes;active or uncontrolled infection; acute or chronic liver disease (i.e., hepatitis, cirrhosis);confirmed diagnosis of HIV infection; or, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia.
  • Patients with history of autoimmune disease.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I / II Study of the Combination of Doxycycline With Temozolomide and Ipilimumab in Patients With Metastatic Melanoma

The goal of this clinical research study is to find the highest tolerable dose of doxycycline that can be combined with temozolomide and ipilimumab in patients with advanced melanoma. The safety and level of effectiveness of the study drug combination will also be studied.

Doxycycline is designed to treat bacterial infection. It also blocks a protein called iNOS that is important in tumor cell growth, which may slow the growth of or kill cancer cells.

Read more

Temozolomide is designed to stop cancer cells from making new DNA (the genetic material of cells). This may stop the cancer cells from dividing into new cells.

Ipilimumab is designed to block the activity of cells that decrease the immune system's ability to fight cancer.

Read the detailed description

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 5 groups of 3-6 participants will be enrolled in the Phase I portion of the study, and up to 28 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of doxycycline you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of doxycycline. Each new group will receive a higher dose of doxycycline than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of doxycycline is found.

If you are enrolled in the Phase II portion, you will receive doxycycline at the highest or most clinically active dose that was tolerated in the Phase I portion.

All participants will receive the same dose level of temozolomide and ipilimumab.

Study Drug Administration:

You will start taking doxycycline on Day -6 of Cycle 1 (1 week before Day 1 of Cycle 1 starts) by mouth 2 times a day by itself for 1 week. You should fast (not eat or drink anything but water) for at least 2 hours before and 1 hour after you take the study drug.

After that, on Day 1 of Cycle 1, you will start taking the combination of temozolomide and ipilimumab. You will receive ipilimumab by vein over 90 minutes every 3 weeks.

On Day 1 of Cycle 1, you will start taking temozolomide by mouth with about 1 cup (8 ounces) of water on Days 1-4 of each cycle. You should fast for at least 2 hours before and 2 hours after you take the study drug.

You will continue taking doxycycline by mouth 2 times a day throughout the study.

Each study cycle is 3 weeks except the first cycle, which is 4 weeks. This is because it includes 1 week of doxycycline given by itself.

You will be given a study drug diary to record the times and doses that you take the study drugs. You should bring the diary to each study visit. You should also bring any leftover study drug with you to each study visit.

Study visits:

At every study visit, you will be asked about any drugs you may be taking, how you are feeling, and if you have had any side effects.

On Day -6 of Cycle 1:

  • You will have a physical exam if not done in the past 8 days.
  • Your weight and vital signs will be measured.
  • Your performance status will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests if this was not done in the past 8 days.
  • Blood (about 4 tablespoons) will be drawn for biomarker testing. Biomarkers are found in the blood and tissue and may be related to your reaction to the study drugs.

On Day 1 of Cycles 1 and 2:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 5 tablespoons) will be drawn for routine tests and biomarker testing.
  • You will have an ECG.
  • On Day 1 of Cycle 1, if you are in Phase II of the study, you will have a tumor biopsy performed to test if doxycycline is able to block the iNOS protein. This biopsy is optional if you are in Phase I.

On Day 8 of Cycle 1, if you are in Phase I:

  • Blood (about 5 tablespoons) will be drawn for routine tests and biomarker testing.
  • Your vital signs will be measured.
  • Your performance status will be recorded.

On Day 15 of Cycle 1, if you are in Phase I, blood (about 5 tablespoons) will be drawn for routine tests and biomarker testing.

On Day 1 of Cycles 3 and beyond:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests.

Every 6 weeks (2 cycles), you will have a CT scan, an MRI scan, and/or a bone scan to check the status of the disease.

Length of Treatment:

You may continue taking doxycycline for as long as the doctor thinks it is in your best interest. You may continue receiving temozolomide and ipilimumab for up to 4 cycles.

You will no longer be able to take the study drugs if the disease gets worse, if you start having other health problems, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment visit.

End-of-Treatment Visit:

Within 4 weeks after your last dose of study drugs:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • Blood (about 5 tablespoons) will be drawn for routine tests and biomarker testing.
  • You will have an ECG.
  • You will have a tumor biopsy performed to test if there is any change in the level of iNOS protein.

This is an investigational study. Temozolomide is FDA approved and commercially available to treat advanced brain tumors. It is commonly used to treat advanced melanoma but is not FDA approved for it. Ipilimumab is FDA approved and commercially available to treat advanced melanoma. Doxycycline is FDA approved and commercially available to treat various infections, but using it to treat cancer is investigational.

Up to 58 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions
Melanoma
Keywords
Melanoma, Metastatic Melanoma, Advanced melanoma, Doxycycline, Ipilimumab, Yervoy, MDX010, BMS-734016, Temozolomide, Temodar
Medical subject headings
Melanoma

What participants receive

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

  • DoxycyclineDrug

    Phase I Starting Dose: 200 mg by mouth twice a day on Day -6 of Cycle 1 (1 week before Day 1 of Cycle 1 starts)

    Phase II Starting Dose: Maximum Tolerated Dose (MTD) from Phase I.

  • IpilimumabDrug

    Also called Yervoy, BMS-734016, MDX010

    Phase I and II: 3 mg by vein on Day 1 of each 21 day cycle for 4 cycles.

  • TemozolomideDrug

    Also called Temodar

    Phase I and II: 200 mg/m2 by mouth on Days 1 - 4 of each 21 day cycle for 4 cycles.

Study groups in NCT01590082
Study groupRoleWhat they receive
Doxycycline, Ipilimumab, and TemozolomideExperimentalDoxycycline to start on day -6 of Cycle 1 (1 week before Day 1 of Cycle 1 starts) twice a day until morning of Day 1 of Cycle 1. After the Day 1 of Cycle 1, participants receive first dose of Ipilimumab, and evening of same day, Temozolomide received by mouth once a day for 4 days. Doxycycline administration will continue twice daily for rest of cycle without interruption; Cycle 1 is 4 weeks of treatment. Starting Cycle 2, Doxycycline with temozolomide and ipilimumab administration start on Day 1. Each cycle is 3 weeks. 4 cycles of therapy given over a 3 month period to complete induction phase. After induction therapy, participants continue on Doxycycline.
Receives: Drug: Doxycycline; Drug: Ipilimumab; Drug: Temozolomide

What is being measured

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

  1. Overall Participant Response

    Number of participants with response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Complete Response (CR): Disappearance all target lesions; Any pathological lymph nodes must be <10mm in short axis. Partial Response (PR): >30% decrease in sum of diameters of target lesions, reference baseline sum of diameters (e.g. percent change from baseline). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for progressive disease. Progressive Disease (PD): >20% increase in sum of diameters of target lesions, reference smallest sum of diameters recorded since treatment started (e.g. percent change from nadir, where nadir defined as smallest sum of diameters recorded since treatment start). In addition, sum must have an absolute increase from nadir of 5mm. Not Applicable (NA): No target lesions at baseline. Not Evaluable (NE): Cannot be classified by 1 of 5 preceding definitions.

    Measured: 2 cycles, up to 7 weeks

Timeline

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

  1. First posted2 May 2012 (estimated)
  2. Study startNov 2012
  3. Primary completionJul 2015
  4. Study completionJul 2015

Why it stopped: Accrual slow due to alternate trials and treatment options.

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01590082
Sponsor's protocol ID
2011-1165
Other IDs
NCI-2014-01836
Status last verified
Aug 2020
First submitted
30 Apr 2012
Last updated
2 Sep 2020
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Doxycycline, Ipilimumab and Temozolomide in people with Melanoma, 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: stopped early, as of the sponsor's last update on 2 Sep 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 combined 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.

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 2 Sep 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?

Overall Participant Response (time frame: 2 cycles, up to 7 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 NCT01590082.

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 2 Sep 2020; AzTrials last refreshed its copy on 6 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in