Clinical trial NCT00734305: Phase I Safety Study of the Drug MM-121 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment
Official title: A Phase I and Pharmocologic Study of MM-121 in Patients With Refractory Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: cancer, solid tumors, oncology, Phase I, ErbB3, HER3
(erbB-3, HER-3)
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2008-08-14
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study was a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design to determine maximum tolerated dose/recommended Phase 2 dose.

Detailed description: Successive cohorts of three or more patients were treated at escalating doses until a maximum tolerated dose/recommended phase 2 dose was identified. The study initially explored a dosing schedule every 7-days, which may have been modified to longer intervals under certain circumstances but did not expand to more than weekly. When the maximum tolerated dose/recommended Phase 2 dose was identified, an Expansion Cohort was enrolled at that dose to further characterize safety and to explore pharmacodynamic endpoints. There were 3 sites that participated.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed advanced solid tumors that have recurred or progressed following standard therapy, or that have not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
* Patients must be \> 18 years of age
* Patients or their legal representatives must be able to understand and sign an informed consent form
* Patients must have evaluable or measurable tumor(s)

  * Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for patients with known peripheral neuropathy.
  * 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 90 days following the last dose of MM-121 (an effective form of contraception is an oral contraceptive or a double barrier method)

In addition, patients to be enrolled the Expansion Cohort must have/be:

* Advanced/metastatic breast cancer with histological/cytological documentation of ER-, PR-, Her2/neu non-over-expressing breast cancer (triple negative breast cancer); OR,
* Patients must have advanced/metastatic breast cancer with histologically or cytologically confirmed ER+ and/or PR+, Her2/neu non-over-expxressing OR,
* Patients must have advanced/metastatic histological confirmation of epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer; OR,
* Additional tumor types such as metastatic colorectal, advanced non small cell lung cancer, and others may be considered on a per-patient basis
* Tumor tissue amenable to biopsy
* Platelet counts, partial thromboplastin time (PTT) and international normalized ratio (INR) within normal limits.
* Willing to undergo tumor biopsy twice (once before and once after treatment with MM-121)
* Blocks of archived formalin-fixed, paraffin-embedded, unstained tumor tissue available for submission. Patients with no available archived tumor tissue available must receive Sponsor approval prior to enrollment.

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 CNS malignancies (primary or metastatic); 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
* NYHA Class III or IV congestive heart failure or LVEF \< 55%
* Known HIV, hepatitis B or C (active, previously treated or both)

Primary outcomes:
measure: Objective Response Rate and Duration
timeFrame: Time from first dose to date of progression, with a median of 7.1 weeks
measure: Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
timeFrame: From date of first dose to 30 days after termination, the longest 47 weeks
Secondary outcomes:
measure: To Describe the Dose-limiting Toxicity of MM-121 as a Monotherapy
timeFrame: From date of first dose to 30 days after termination, the longest 47 weeks
measure: To Determine the Pharmacokinetic and Immunogenicity Parameters of MM-121
timeFrame: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
measure: To Determine the Pharmacokinetic Parameters of MM-121
timeFrame: At Cycle 1, Week 1 pre-treatment, at the end of the infusion, and 2, 4, 8, 24, 48 and 72 hours after starting the infusion; pre-dose collections on Cycle 1, Week 2 and Cycle 2, Week 1 for all patients
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville,
country: United States
facility: The Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Fox Chase Cancer Center
name: Crystal Denlinger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana-Farber Cancer Institute
name: Kwok Kin Wong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Keedy L Vicki, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Denlinger CS, Keedy VL, Moyo V, MacBeath G, Shapiro GI. Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Invest New Drugs. 2021 Dec;39(6):1604-1612. doi: 10.1007/s10637-021-01145-y. Epub 2021 Jul 11.