Phase I Safety Study of the Drug MM-121 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment

NCT ID: NCT00734305

Last Updated: 2016-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2013-09-30

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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation

Cohorts of escalating doses of MM-121 administered IV QW to determine MTD or RP2D + expansion cohort at MTD/RP2D

Group Type: EXPERIMENTAL

MM-121

Intervention Type: DRUG

Dose escalation Frequency - once weekly

Interventions

MM-121

Dose escalation Frequency - once weekly

Intervention Type: DRUG

Other Intervention Names

Seribantumab, SAR256212

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Merrimack Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Crystal Denlinger, MD

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Kwok Kin Wong, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Keedy L Vicki, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

The Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34250553 (View on PubMed)

Other Identifiers

MM-121

Identifier Type: -

Identifier Source: secondary_id

MM-121-01-100

Identifier Type: -

Identifier Source: org_study_id