MEDI-573 in Combination With SOC in Unresectable or Metastatic HCC.

Browse trials for

• Carcinoma 6,745
• Carcinoma, Hepatocellular 3,180

Keywords

• HCC, liver cancer, hepatocellular carcinoma, MEDI-573, anti-IGF

Carcinoma

6,745 studies on the registry are indexed under Carcinoma; 1,163 are open to participants now.

This study's enrollment of 6 is below the median of 45 across 5,174 interventional studies indexed under Carcinoma.

Lead sponsor

MedImmune LLC is the lead sponsor of 265 studies on the registry; none are open to participants now.

Of its 50 completed or terminated interventional studies of FDA-regulated products, 28 (56%) have results posted.

Study arms

• Experimental
  Phase 1b Cohort A

  Participants will receive MEDI-573 10 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.

  Drug: MEDI-573 (1 of 3 doses) · Drug: Sorafenib

• Experimental
  Phase 1b Cohort B

  Participants will receive MEDI-573 45 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.

  Drug: MEDI-573 (1 of 3 doses) · Drug: Sorafenib

• Experimental
  Phase 1b Cohort C

  Participants will receive MEDI-573 30 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.

  Drug: MEDI-573 (1 of 3 doses) · Drug: Sorafenib

• Experimental
  Phase 2 Arm 1

  Participants will receive recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.

  Drug: MEDI-573 (1 of 3 doses) · Drug: Sorafenib

• Active comparator
  Phase 2 Arm 2

  Participants will receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.

  Drug: Sorafenib

Interventions

• DrugMEDI-573 (1 of 3 doses)

  MEDI-573, a human immunoglobulin G2 lambda (IgG2λ) monoclonal antibody (MAb), is a dual-targeting human antibody that neutralizes insulin-like growth factor (IGF)-I and IGF-II ligands

• DrugSorafenib

  Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor

Primary outcomes

1. Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)

   The DLT was defined as any Grade 3 or higher hematologic or non-hematologic toxicity considered to be related to MEDI-573 that occurred during the DLT evaluation period (Days 1 to 21 of Cycle 1), with the exceptions of Grade 3 fever (occurred in the absence of neutropenia and resolved to normal or baseline within 24 hours of treatment and was not considered as SAE), Grade 3 rigors/chills that responded to optimal therapy, and Grade \< 4 hyperglycemia that resolved in \< 24 hours.

   Time frame: Day 1 to Day 21 of Cycle 1

2. Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)

   An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).

   Time frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)

3. Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs

   An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).

   Time frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)

4. Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs

   An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).

   Time frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)

5. Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs

   An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).

   Time frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)

6. Phase 2: Time to Progression

   Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

   Time frame: From Day 1 until documentation of progressive disease (approximately 15 months)

Secondary outcomes

1. Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573

   Participants with positive ADA to MEDI-573 are reported in the below table. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.

   Time frame: Predose on Day 1 of every treatment cycle; end of treatment; Days 30, 60 and 90 post treatment; every 3 months post treatrment till end of study (approximately 15 months)

2. Phase 2: Best Overall Tumor Response

   Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

   Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)

3. Phase 2: Objective Response Rate

   Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

   Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)

4. Phase 2: Progression-free Survival (PFS)

   Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

   Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)

5. Phase 2: Change in Tumor Size

   Phase 2 part the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.

   Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)

6. Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1

   The tmax is defined as actual sampling time to reach maximum observed serum concentration of the study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.

   Time frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)

7. Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1

   The Cmax is the maximum observed serum concentration of study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.

   Time frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)

8. Phase 1b and Phase 2: Area Under Serum Concentration-time Curve From Time Zero to Day 22 (AUC0-Day22) of MEDI-573 for Cycle 1

   Area under the concentration-time curve from time zero to Day 22 is reported. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.

   Time frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)

Baseline characteristics