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HER-2 Gene AmplificationPhase 1NCT01304784

A Study of MM-111 in Combination With Multiple Treatments in Patients With HER2 Positive Cancer

A Phase 1 study testing Cisplatin, Capecitabine, Trastuzumab and MM-111, Lapatinib +/- Trastuzumab and MM-111 and Paclitaxel, Trastuzumab and MM-111 in people with HER-2 Gene Amplification, run by Merrimack Pharmaceuticals at 15 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

This study is an open-label, dose-escalation study of MM-111 with five different combination treatments with the main goal of determining the safety of MM-111 with each combination. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HER-2 Gene Amplification
What is being tested?
Cisplatin, Capecitabine, Trastuzumab and MM-111, Lapatinib +/- Trastuzumab and MM-111 and Paclitaxel, Trastuzumab and MM-111
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
15 sitesUnited States
Study dates
Jan 2011to Jun 2014
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

  • Patients must have histologically or cytologically confirmed advanced cancer that is positive for HER2, either:
  • At least 3+ positive by immunohistochemistry, or
  • Gene amplified positive by fluorescence in situ hybridization (FISH). Chromogenic in situ hybridization (CISH) is acceptable to confirm HER2 positivity if FISH results are not available.
  • The patient's cancer must have recurred or progressed following standard therapy or have not responded to standard therapy. (Patients with previously untreated HER2+ metastatic gastric or gastro-esophageal junction cancer can be enrolled onto the cisplatin, capecitabine, and trastuzumab + MM-111 arm of the study.)
  • Patients must be ≥ 18 years of age.
  • Patients or their legal representatives must be able to understand and sign an informed consent.
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  • Patients should have evaluable or measurable disease ≥ 1 cm.
  • Patients must have ECOG PS ≤ 1 or Karnofsky performance score of ≥ 70.
  • Patients must have adequate hematologic status as evidenced by:
  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
  • Platelet count ≥ 100,000 platelets/mm3
  • Hemoglobin ≥ 9 g/dL
  • For arms 1, 2, 3 and 4 patients must have adequate hepatic function as evidenced by:
  • Serum total bilirubin ≤ 1.5 × the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 x ULN (5 × ULN is acceptable if liver metastases are present)
  • For arm 5 (Docetaxel) patients must have adequate hepatic function as evidenced by:
  • Serum bilirubin within normal limits,
  • AST and/or ALT < 1.5 X ULN and alkaline phosphatase < 2.5 X ULN if concomitantly elevated
  • Patients must have adequate renal function as evidenced by:
  • Serum creatinine ≤ 1.5 × ULN
  • Calculated clearance 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v.4.0) up to Grade 1 is acceptable for patients with pre-existing peripheral neuropathy.
  • Patients must have a life expectancy of at least 3 months. Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 60 days following the last dose of MM-111.

Who cannot join

  • Patients for whom potentially curative antineoplastic therapy is available
  • Patients who are pregnant or lactating
  • Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the Investigator, patients with tumor fever may be enrolled.)
  • Patients with untreated and/or symptomatic primary or metastatic central nervous system (CNS) malignancies (Patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial.)
  • Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies.
  • Patients with a known history of hypersensitivity to any of the drug components of a particular regimen.
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  • Patients who have received other recent antitumor therapy including:
  • Investigational therapy administered within the 28 days prior to the first scheduled day of dosing MM-111. Dosing in < 28 days since receiving investigational therapy is acceptable once a time interval equal to at least five half-lives of the investigational agent have passed.
  • Any standard chemotherapy or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of MM-111.
  • There is no necessary washout for trastuzumab. Patients enrolled to the lapatinib-containing arms of the study do not need to have a washout period for lapatinib.
  • Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%
  • History of myocardial infarction within 12 months of enrollment
  • Uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg)
  • Known angina pectoris requiring medication
  • Known clinically significant valvular heart disease
  • Known history of high-risk arrhythmias
  • Known history of congestive heart failure
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
  • Active gastrointestinal bleedingPatients who have received prior maximum cumulative anthracycline doses:
  • doxorubicin or liposomal doxorubicin doses > 360 mg/m2
  • mitoxantrone > 120 mg/m2 and idarubicin > 90 mg/m2
  • epirubicin doses higher than 720 mg/m2
  • Other (e.g., liposomal doxorubicin or other anthracycline equivalent of 360 mg/m2 of doxorubicin)
  • If more than 1 anthracycline has been used, the cumulative dose must not exceed the equivalent of 360mg/m2 of doxorubicin
  • Patients with a history of allogeneic transplant. (Patients with a history of autologous bone marrow or stem cell transplant may be enrolled.)
  • Patients with known human immunodeficiency virus (HIV), hepatitis B or C. (If patients have previously been treated for hepatitis C and have undetectable viral loads, they can be considered eligible for the trial.)
  • Patients with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • New York Oncology/Hematology

    Albany, New York, 12206

  • Georgia Cancer Specialists

    Atlanta, Georgia, 30342

  • Texas Oncology Cancer Center

    Austin, Texas, 78731

  • Texas Oncology PA North/Sammans Cancer Center

    Dallas, Texas, 75246

  • Rocky Mountain Cancer Centers

    Denver, Colorado, 80218

  • GHS Institute of Transitional Oncology Research

    Greenville, South Carolina, 29605

  • Central Indiana Cancer Centers

    Indianapolis, Indiana, 46151

  • Innovation Center - Kettering Medical Center Health Network

    Kettering, Ohio, 45429

  • Horizon Oncology Research, Inc

    Lafayette, Indiana, 47908

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89135

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Evergreen Hematology and Oncology

    Spokane, Washington, 99218

  • Texas Oncology - Tyler

    Tyler, Texas, 75702

  • Northwest Cancer Specialists-Vancouver Cancer Center

    Vancouver, Washington, 98684

Other trials in United States

About this study

Official title: A Phase 1 and Pharmacologic Study of MM-111 in Combination With Multiple Treatment Regimens in Patients With Advanced HER2 Positive Solid Tumors

This study is an open-label, dose-escalation study of MM-111 with five different combination treatments with the main goal of determining the safety of MM-111 with each combination.

Read the detailed description

To determine the MTD and any DLT of MM 111 when administered in combination with either 1) cisplatin, capecitabine, and trastuzumab; 2) lapatinib +/- trastuzumab; 3) paclitaxel and trastuzumab 4) lapatinib, paclitaxel and trastuzumab or 5) docetaxel and trastuzumab in patients with human epidermal growth factor receptor (HER2+) solid tumors

Being tested
Cisplatin, Capecitabine, Trastuzumab and MM-111, Lapatinib +/- Trastuzumab and MM-111, Paclitaxel, Trastuzumab and MM-111, Lapatinib, trastuzumab, paclitaxel, and MM-111, Docetaxel, trastuzumab and MM-111
Keywords
Solid tumors, Failed at least one line of standard therapy

What participants receive

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

  • Cisplatin, Capecitabine, Trastuzumab and MM-111Drug

    Also called Capecitabine = Xeloda, Trastuzumab = Herceptin

    Conventional chemotherapy

  • Lapatinib +/- Trastuzumab and MM-111Drug

    Also called Trastuzumab = Herceptin, Lapatinib = Tykerb

    Conventional chemotherapy

  • Paclitaxel, Trastuzumab and MM-111Drug

    Also called Trastuzumab = Herceptin, Paclitaxel = Taxol

    Conventional chemotherapy

  • Lapatinib, trastuzumab, paclitaxel, and MM-111Drug

    Also called Trastuzumab = Herceptin, Paclitaxel = Taxol, Lapatinib = Tykerb

    Conventional chemo

  • Docetaxel, trastuzumab and MM-111Drug

    Also called Trastuzumab = Herceptin, Docetaxel = Taxotere

    Conventional chemotherapy

Study groups in NCT01304784
Study groupRoleWhat they receive
Arm 1ExperimentalRegimen follows a 3-week treatment cycle. Cisplatin 80mg/m2 given on day 1 by IV infusion over two hours every three weeks. Capecitabine 1000 mg/m2 given orally twice daily for fourteen days each 3-week cycle. Up to six 3-week cycles of Cisplatin and Capecitabine to be administered. Trastuzumab given as 8 mg/kg loading dose at week 1 over 90 minutes followed by 6 mg/kg every 3 weeks over 30-90 minutes. MM-111 will be administered over 90 minutes for the first infusion and then weekly over 60 minutes thereafter. Trastuzumab (every 3 weeks) and MM-111 (weekly) will continue until disease progression, unacceptable toxicity, or withdrawal of consent.
Receives: Drug: Cisplatin, Capecitabine, Trastuzumab and MM-111
Arm 2ExperimentalRegiment follows a 4-week treatment cycle. The following Lapatinib and Trastuzumab regimen will be given in combination with MM-111 in the following order: * Trastuzumab 4 mg/kg loading dose week 1 over 90 minutes * Followed by Trastuzumab 2 mg/kg weekly thereafter * Lapatinib 1000 mg by mouth (PO) daily * MM-111 will be administered over 90 minutes for the first infusion and then weekly over 60 minutes thereafter Treatment with this regimen will be continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Receives: Drug: Lapatinib +/- Trastuzumab and MM-111
Arm 3ExperimentalRegimen follows a 4-week treatment cycle Paclitaxel dosing should begin first dose on cycle 1 day 1. Paclitaxel will be administered at 80 mg/m2 weekly, as an IV infusion over 60 minutes. The infusion should be prepared as directed in the Paclitaxel package insert. All patients receiving Paclitaxel should be premedicated as per the local institutional guidelines. Trastuzumab will be administered via IV over 90 minutes at a 4 mg/kg loading dose for the first infusion followed by weekly infusion of 2 mg/kg over 60 minutes thereafter. MM-111 will be administered over 90 minutes for the first infusion and then weekly over 60 minutes thereafter. Treatment with this regimen will be continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Receives: Drug: Paclitaxel, Trastuzumab and MM-111
Arm 4Experimental4-week treatment cycle. Lapatinib given orally. Paclitaxel dosing on cycle 1 day 1. Paclitaxel given at 80 mg/m2 weekly, as an IV infusion over 60 minutes. The infusion should be prepared as directed in the Paclitaxel package insert. All patients receiving Paclitaxel should be premedicated as per the local institutional guidelines. Trastuzumab given via IV over 90 minutes at a 4 mg/kg loading dose for the first infusion followed by weekly infusion of 2 mg/kg over 60 minutes thereafter. MM-111 given over 90 minutes for the first infusion and then weekly over 60 minutes thereafter. Treatment with this regimen will be continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Receives: Drug: Lapatinib, trastuzumab, paclitaxel, and MM-111
Arm 5ExperimentalDocetaxel, trastuzumab and MM-111 3-week treatment cycles with therapies given in the following order: 1) docetaxel, 2) trastuzumab, and 3) MM-111 Docetaxel given as an IV infusion over 60 minutes every three weeks. The infusion should be prepared as directed in the Docetaxel package insert and any institutional guidelines. All patients receiving Docetaxel should be pre-medicated as per the local institutional guidelines. The first dose of trastuzumab is a loading dose of 8 mg/kg administered over 90 minutes followed by every three week dosing at 6 mg/kg over 60 minutes via IV infusion. The first dose of MM-111 given over 90 minutes followed by 3 week dosing over 60 minutes in the absence of infusion-related reactions
Receives: Drug: Docetaxel, trastuzumab and MM-111

What is being measured

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

  1. Determine patient's safety (# of adverse events/serious adverse events) and tolerability of MM-111 in combination with multiple treatment regimens

    To determine the maximum tolerated dose (MTD) and any dose limiting toxicity (DLT) of MM-111 when administered in combination with either 1. cisplatin, capecitabine, and trastuzumab; 2. lapatinib +/- trastuzumab; 3. paclitaxel and trastuzumab 4. lapatinib, paclitaxel, trastuzumab; or 5. docetaxel and trastuzumab in patients with HER 2 positive solid tumors

    Measured: 30 months

Secondary outcomes (2)

  1. To characterize the pharmacokinetics (PK) profile of MM-111 when administered in combination with multiple treatment regimens. The PK profile will help to determine the phase 2 dose

    Treatment regimens include either: 1. cisplatin, capecitabine, and trastuzumab; 2. lapatinib +/- trastuzumab; 3. paclitaxel and trastuzumab; 4. lapatinib, paclitaxel, trastuzumab; or 5. docetaxel and trastuzumab in patients with HER2+ solid tumors.

    Measured: 33 months

  2. To establish the recommended Phase 2 dose(s) of MM-111 when administered in each of the combinations assessed (based on PK profile, safety data and overall patient tolerability)

    Measured: 33 months

Timeline

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

  1. First posted25 Feb 2011 (estimated)
  2. Study startJan 2011
  3. Primary completionApr 2014
  4. Study completionJun 2014

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01304784
Sponsor's protocol ID
MM-111-01-01-03
Status last verified
Dec 2015
First submitted
17 Feb 2011
Last updated
16 Dec 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cisplatin, Capecitabine, Trastuzumab and MM-111, Lapatinib +/- Trastuzumab and MM-111 and Paclitaxel, Trastuzumab and MM-111 in people with HER-2 Gene Amplification, run by Merrimack Pharmaceuticals at 15 sites 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 23 inclusion and 27 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 16 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites 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?

Determine patient's safety (# of adverse events/serious adverse events) and tolerability of MM-111 in combination with multiple treatment regimens (time frame: 30 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 NCT01304784.

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 16 Dec 2015.

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