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

HER-2 Gene Amplification Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01304784
• Other study ID #: MM-111-01-01-03
• Status: Completed
• Phase: Phase 1
• First received: February 17, 2011
• Last updated: December 15, 2015
• Start date: January 2011
• Est. completion date: June 2014

Study information

• Verified date: December 2015
• Source: Merrimack Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: June 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• 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.

• 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.

Exclusion Criteria:

• 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.

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HER-2 Gene Amplification

Intervention

Drug:
• Cisplatin, Capecitabine, Trastuzumab and MM-111
Conventional chemotherapy
• Lapatinib +/- Trastuzumab and MM-111
Conventional chemotherapy
• Paclitaxel, Trastuzumab and MM-111
Conventional chemotherapy
• Lapatinib, trastuzumab, paclitaxel, and MM-111
Conventional chemo
• Docetaxel, trastuzumab and MM-111
Conventional chemotherapy

Locations

Country	Name	City	State
United States	New York Oncology/Hematology	Albany	New York
United States	Georgia Cancer Specialists	Atlanta	Georgia
United States	Texas Oncology Cancer Center	Austin	Texas
United States	Texas Oncology PA North/Sammans Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	GHS Institute of Transitional Oncology Research	Greenville	South Carolina
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Innovation Center - Kettering Medical Center Health Network	Kettering	Ohio
United States	Horizon Oncology Research, Inc	Lafayette	Indiana
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Evergreen Hematology and Oncology	Spokane	Washington
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Northwest Cancer Specialists-Vancouver Cancer Center	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Merrimack Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	30 months	Yes
Secondary	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.	33 months	Yes
Secondary	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)		33 months	Yes