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Triple Negative Breast CancerPhase 1NCT00998036

Study of Temsirolimus, Erlotinib and Cisplatin in Solid Tumors

A Phase 1 study testing Temsirolimus, Cisplatin and Erlotinib in people with Triple Negative Breast Cancer, run by Columbia University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase I research study designed to determine the maximum tolerated dose (MTD) of cisplatin, temsirolimus, and erlotinib in combination for treatment in triple negative breast cancer (TNBC) patients. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
Temsirolimus, Cisplatin and Erlotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
Sep 2009to 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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which the combination of cisplatin, temsirolimus, and erlotinib is a reasonable treatment.
  • Patients with measurable or non-measurable disease are eligible for entry to this study. Tumor markers may be considered non-measurable disease.
  • Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. No chemotherapy or radiotherapy may be given within 3 weeks prior to the start of protocol treatment.
  • Patients must be ≥18 years old.
  • Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1
  • Life expectancy of greater than 12 weeks.
Show all 11Show fewer
  • Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
  • Required Laboratory Values: absolute neutrophil count (ANC) ≥1,500/mm3, platelets ≥100,000/mm3, hemoglobin ≥9.0 g/dL, total bilirubin ≤1.5 x upper limit of normal (ULN), aspartate transaminase (AST)/alanine transaminase (ALT) ≤3.0 x ULN, alkaline phosphatase ≤2.5 x ULN, creatinine ≤2.0 x ULN OR Patients must have either a normal serum creatinine (<= IULN) OR estimated creatinine clearance 60 ml/min (Cockcroft-Gault formula) within 28 days prior to registration. Prothrombin time (PT)/INR ≤1.5, unless the patient is on full dose warfarin or stable dose of low-molecular-weight (LMW) heparin with a therapeutic INR of >1.5 - ≤3. Patients with triglyceride levels >400 mg/dL can be started on lipid lowering agents and reevaluated within 1 week. If levels go to ≤400 mg/dL, they can be considered for the trial and continue the lipid lowering agents.
  • Concomitant Medications: Temsirolimus and Erlotinib are primarily metabolized by CYP3A4. Patients CANNOT be receiving enzyme-inducing or enzyme inhibiting agents listed here: Inhibitors: Amiodarone, Amprenavir, Atazanavir, Chloramphenicol, Clarithromycin, Conivaptan, Cyclosporine, Darunavir, Dasatinib, Delavirdine, Diltiazem, Erythromycin, Fluconazole, Fluoxetine, Fluvoxamine, Fosamprenavir, Imatinib, Indinavir, Isoniazid, Itraconazole, Ketoconazole, Lapatinib, Miconazole, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Quinupristin, Saquinavir, Tamoxifen, Telithromycin, Troleandomycin, Verapamil, Voriconazole. Inducers: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John's wort, Sulfadimidine, Sulfinpyrazone, Troglitazone, Troleandomycin. All concomitant medications must be recorded. Patients also must agree to refrain from drinking grapefruit juice while on study.
  • Sexually Active Patients: For all sexually active patients, the use of adequate contraception (hormonal or barrier method of birth control) will be required prior to study entry and for the duration of study participation. Non-pregnant status will be determined in all women of childbearing potential.
  • Patients must have signed an approved informed consent.

Who cannot join

  • More than 3 prior chemotherapy treatments for metastatic disease.
  • Patients receiving anti-retroviral therapy (HAART) for HIV infection because of possible pharmacokinetic interactions.
  • Active central nervous system (CNS) disease
  • Any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.
  • Patients pregnant or nursing.
  • Patients who have used tobacco or nicotine products containing medications within the last three months given their significant effect on erlotinib drug levels.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

About this study

Official title: Phase I Study of Combined Temsirolimus, Erlotinib and Cisplatin in Advanced Solid Tumors

This is a Phase I research study designed to determine the maximum tolerated dose (MTD) of cisplatin, temsirolimus, and erlotinib in combination for treatment in triple negative breast cancer (TNBC) patients.

Read the detailed description

The stratification of breast cancer patients for treatment targeting either the estrogen receptor (ER) or human epidermal growth factor receptor 2 (HER2) receptor based upon the measurement of ER/progesterone receptor (PR) and HER2 in tumor tissue has changed the treatment of breast cancer. However, the success of this stratification has resulted in the recognition that no effective rational treatment exists for patients that lack these receptors. The term "triple negative breast cancer" (TNBC) has been used to define a class of unresponsive patients, which is based upon their lack of the hormone receptors for estrogen and progesterone and the HER2 oncogene. TNBC represents a form of breast cancer for which no targeted therapy is known.

Thus, identifying and understanding the signaling pathways and receptors that contribute to triple negative tumor growth is of high priority in order to develop therapies analogous to the ones that have already been developed for HER2 and ER.

Available data from Phase I trials have demonstrated that mTOR inhibitors and EGFR inhibitors have been safely given together at doses shown to inhibit their respective targets and Phase II studies are ongoing in advanced renal cell, pancreatic, glioma, and breast (not specifically TNBC) cancers.

The rationale for adding cisplatin to erlotinib and an mTOR inhibitor are many. Cisplatin is a known active cytotoxic against breast cancer. It has non overlapping toxicity with erlotinib and TORC1 mTOR inhibitors and patients are unlikely to have been previously treated with cisplatin. Therefore, as a cytotoxic DNA damaging agent, cisplatin could trigger cell death in a cell whose survival pathways are effectively inhibited by mTOR inhibition and erlotinib.

Being tested
Temsirolimus, Cisplatin, Erlotinib
Keywords
TNBC, Temsirolimus, Erlotinib, Cisplatin, Breast Cancer
Medical subject headings
Triple Negative Breast Neoplasms, Breast Neoplasms

What participants receive

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

  • TemsirolimusDrug

    Also called Torisel

    Temsirolimus will be administered intravenously weekly on days one and eight of a three week cycle. Temsirolimus will not be given on week three (usually dosed weekly) for increased tolerability given its possible plasma accumulation during week three. Temsirolimus will be given second over a 30 minute infusion during posthydration.

    Dose escalation will follow the standard 3 by 3 design with three set dosing levels.

    Dose Level 1: Temsirolimus 15mg

    Dose Level 2: Temsirolimus 15mg

    Dose Level 3: Temsirolimus 25mg

  • CisplatinDrug

    Also called Platinol

    Cisplatin at 30mg/m2 will be administered intravenously weekly on days one and eight of a three week cycle. Cisplatin will be given first over a 30 minute infusion with prehydration.

  • ErlotinibDrug

    Also called Tarceva

    Erlotinib will be taken by mouth daily starting at 100mg. On days of cisplatin and temsirolimus infusions, erlotinib should be taken at least two hours after the beginning of the temsirolimus infusion.

    Dose escalation will follow the standard 3 by 3 design with three set dosing levels.

    Dose Level 1: Erlotinib 100mg

    Dose Level 2: Erlotinib 150mg

    Dose Level 3: Erlotinib 150mg

Study groups in NCT00998036
Study groupRoleWhat they receive
Temsirolimus, cisplatin, erlotinibExperimentalCisplatin and temsirolimus will be administered weekly on days one and eight of a three week cycle. Erlotinib will be taken by mouth daily.
Receives: Drug: Temsirolimus; Drug: Cisplatin; Drug: Erlotinib

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Cisplatin

    MTD of the drug as part of combination therapy will be determined.

    Measured: 6 months

  2. MTD of Temsirolimus

    MTD of the drug as part of combination therapy will be determined.

    Measured: 6 months

  3. MTD of Erlotinib

    MTD of the drug as part of combination therapy will be determined.

    Measured: 6 months

Timeline

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

  1. First posted20 Oct 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionJun 2012
  4. Study completionOct 2012

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00998036
Sponsor's protocol ID
AAAD8279
Status last verified
Dec 2017
First submitted
19 Oct 2009
Last updated
13 Dec 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Temsirolimus, Cisplatin and Erlotinib in people with Triple Negative Breast Cancer, run by Columbia University 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 11 inclusion and 6 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 13 Dec 2017. 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?

Maximum Tolerated Dose (MTD) of Cisplatin (time frame: 6 months). The study lists 3 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 NCT00998036.

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 13 Dec 2017.

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