A Study of MK-8109 (Vintafolide) Given Alone or With Chemotherapy in Participants With Advanced Cancers (MK-8109-001)

NCT01688791 | Terminated Phase 1

• 2 other identifiers: 8109-0012012-002799-14
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial will be conducted in three parts. Part A is a dose escalation trial followed by a dose confirmation trial in folate receptor (FR) 100% endometrial cancer participants. The primary hypothesis of this trial is that administration of vintafolide in combination with carboplatin and paclitaxel is safe and tolerable. Part B is a single dose, dose escalation, pharmacokinetic (PK), and QTc interval trial. The primary objectives include determination of the maximum single tolerated dose of vintafolide and to evaluate the effect of this single maximum dose on the QTc interval. Part C is a weekly dose escalation trial of vintafolide followed by a dose confirmation. The primary hypothesis of this part is that weekly vintafolide has acceptable safety and tolerability in participants with advanced cancers.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (3)

• Parts A and C: Number of participants with dose-limiting toxicities (DLTs)

  Cycle 1 (21 days)

• Part B: Change from Baseline in QTc interval

  30 minutes pre-dose and up to 2 hours post-dose

• Part C: Number of Participants Experiencing an Adverse Event (AE)

  Up to 18 weeks (six 3-week cycles)

Secondary Outcomes (5)

• Number of participants whose best response is partial response (PR) or complete response (CR)

  Week 6

• Progression free survival

  Week 6

• Disease control rate

  Week 6

• Part B: Pharmacokinetics (PK) of vintafolide, including Area Under the Curve (AUC) and Maximum Concentration (Cmax)

  Day 1

• Part B: PK of Vintafolide Metabolites, including AUC and Cmax

  Day 1

Study Arms (3)

Part A: Vintafolide BIW

EXPERIMENTAL

Vintafolide, intravenously (IV), on Days 1, 4, 8, and 11 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m\^2, administered on Day 1 of each 21-day cycle

Drug: Vintafolide; Drug: Carboplatin; Drug: Paclitaxel

Part A: Vintafolide TIW

EXPERIMENTAL

Vintafolide, intravenously (IV) on Days 1, 3, 5, 8, 10, and 12 of each 21-day cycle. Carboplatin, IV, at a dose of area under the curve (AUC)5, administered on Day 1 of each 21-day cycle. Paclitaxel, IV, at a dose of 175 mg/m\^2, administered on Day 1 of each 21-day cycle

Drug: Vintafolide; Drug: Carboplatin; Drug: Paclitaxel

Parts B & C: Vintafolide Single Dose & Weekly (QW)

EXPERIMENTAL

Single dose, dose escalation, vintafolide (Part B) followed by 2 week observation. Those completing Part B will have the option to continue on to Part C (weekly dosing, dose finding, on Days 1, 8, and 15 in a 21-day cycle until disease progression or toxicity) unless they experience severe and/or persistent drug related toxicity.

Drug: Vintafolide

Interventions

Vintafolide DRUG

Also known as: MK-8109, EC-145

Part A: Vintafolide BIW; Part A: Vintafolide TIW; Parts B & C: Vintafolide Single Dose & Weekly (QW)

Carboplatin DRUG

Part A: Vintafolide BIW; Part A: Vintafolide TIW

Paclitaxel DRUG

Part A: Vintafolide BIW; Part A: Vintafolide TIW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist or is unacceptable to the participant
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• At least one measurable metastatic or recurrent lesion
• No history of a previous malignancy with the exception of cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or adequately treated localized prostate carcinoma; or has undergone potentially curative therapy with no evidence of disease for five years
• Adequate organ function
• Female participants of childbearing potential must be willing to use acceptable methods of birth control or abstain from heterosexual activity for the course of the study through 90 days after the last dose of study therapy
• Male participants must agree to use an adequate method of contraception for heterosexual activity starting with the first dose of study therapy through 90 days after the last dose of study therapy
• Tumor lesions characterized as folate receptor (FR) 100% as determined by an etarfolide Sequential Single Photon Emission Computed Tomography (SPECT) and CT scan
• Histologically-confirmed diagnosis of locally advanced or metastatic or recurrent endometrial cancer
• \- Must have an etarfolatide SPECT/CT scan to determine FR status

You may not qualify if:

• Part A \& Part C if enrolled after completion of Part B: Chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to drug administration, or not recovered from adverse events due to agents administered more than 4 weeks earlier
• Part B: Chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 3 weeks prior to drug administration, or not recovered from adverse events due to agents administered more than 4 weeks earlier
• Currently participating or has participated in a study with an investigational compound or device within 28 days of initial dosing on this study
• Part A, dose escalation, Parts B and C: More than 3 prior cytotoxic regimens for metastatic disease.
• Part A, dose confirmation: Has received more than 2 prior cytotoxic regimens for metastatic disease.
• Primary central nervous system (CNS) tumor
• Active CNS metastases and/or carcinomatous meningitis.
• Known hypersensitivity to the components of the study therapy or its analogs
• Recent (i.e., ≤ 6 weeks) history of abdominal surgery or peritonitis
• Bowel occlusion or sub-occlusion
• Prior whole abdominal or whole pelvis radiation therapy or radiation therapy to \>10% of the bone marrow at any time in the past or prior radiation therapy within the last 3 years to the breast / sternum, head, or neck
• Requires anti-folate therapy for the management of co-morbid conditions
• Known regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
• Pregnant or breastfeeding or expecting to conceive, or donate sperm within the span of the study
• Human Immunodeficiency Virus (HIV)-positive

Sponsors & Collaborators

• Endocyte: lead

MeSH Terms

Interventions

EC145; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2012
• First Posted: September 20, 2012
• Study Start: December 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: February 10, 2015

Record last verified: 2015-02