MPACT Study to Compare Effects of Targeted Drugs on Tumor Gene Variations

NCT01827384 | Completed Phase 2 Results DMC FDA Drug

• 6 other identifiers: NCI-2013-01588MPACT130105P1210479149ZIABC011078
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 8

Brief Summary

This phase II trial studies molecular profiling-based assignment of cancer therapy (MPACT) in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Adavosertib, everolimus, and trametinib are drugs that each target a specific variation in tumors by blocking different proteins needed for cell growth. Veliparib blocks an enzyme that helps repair deoxyribonucleic acid (DNA) damaged by chemotherapy, which may help chemotherapy drugs work better. It is not yet known whether testing patients for variations in their tumor and assigning treatment targeting the variation is more effective than standard non-targeted therapy in treating advanced solid tumors.

Conditions

Advanced Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Objective Response

  ORR is the proportion of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all tumors. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  Up to 30 days after completion of study treatment, up to 75 months

Secondary Outcomes (1)

• Proportion of Participants With 4 Month Progression-free Survival (PFS)

  4 months

Other Outcomes (1)

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approx. 73months (m) & 21day (d); 4m & 11d; 61m & 8d; 4m & 11d; 10m & 11d; 72m & 29d; 13m & 11d; 6m & 13d; 29m & 18d; 48m & 25d; 49m & 5d; 4m &7d; 15m & 5d; and 75m &13d, for each group respectively.

Study Arms (4)

Regimen I (veliparib, temozolomide)

EXPERIMENTAL

Patients receive veliparib by mouth (PO) twice a day (BID) on days 1-7 and temozolomide PO every day (QD) on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Temozolomide; Drug: Veliparib

Regimen II (adavosertib, carboplatin)

EXPERIMENTAL

Patients receive adavosertib by mouth (PO) twice a day (BID) for 5 doses starting on day 1 and carboplatin intravenous (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Adavosertib; Drug: Carboplatin

Regimen III (everolimus)

EXPERIMENTAL

Patients receive everolimus by mouth (PO) every day (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Everolimus

Regimen IV (trametinib)

EXPERIMENTAL

Patients receive trametinib by mouth (PO) every day (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Trametinib

Interventions

Adavosertib DRUG

Given by mouth (PO)

Also known as: AZD-1775, AZD1775, MK-1775, MK1775

Regimen II (adavosertib, carboplatin)

Carboplatin DRUG

Given intravenous (IV)

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Regimen II (adavosertib, carboplatin)

Everolimus DRUG

Given by mouth (PO)

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Regimen III (everolimus)

Temozolomide DRUG

Given by mouth (PO)

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Regimen I (veliparib, temozolomide)

Trametinib DRUG

Given by mouth (PO)

Also known as: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212

Regimen IV (trametinib)

Veliparib DRUG

Given by mouth (PO)

Also known as: ABT-888, PARP-1 inhibitor ABT-888

Regimen I (veliparib, temozolomide)

Eligibility Criteria

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

You may qualify if:

• TUMOR BIOPSY SEQUENCING: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy and/or no standard of treatment exists that has been shown to prolong survival
• TUMOR BIOPSY SEQUENCING: Patient must have tumor amenable to percutaneous or excisional skin biopsy and be willing to undergo a tumor biopsy or biopsy samples (formalin-fixed paraffin-embedded \[FFPE\] blocks) collected on another study or from a procedure performed due to medical necessity may be acceptable if collected within 6 months prior to registration on molecular profiling-based assignment of cancer therapy (MPACT) and providing that the patient has not received any investigational or targeted treatment since that time, or a report from a Molecular Analysis for Therapy Choice (MATCH) study designated Clinical Laboratory Improvement Act (CLIA) laboratory that a patient has a variant in the genes of interest
• TUMOR BIOPSY SEQUENCING: Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
• TUMOR BIOPSY SEQUENCING: Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents are eligible to participate and may continue this treatment; patients with prostate cancer may continue luteinizing hormone-releasing hormone (LHRH) agonists or antagonists
• TUMOR BIOPSY SEQUENCING: Karnofsky performance status \>= 70%
• TUMOR BIOPSY SEQUENCING: Life expectancy \> 3 months
• TUMOR BIOPSY SEQUENCING: Absolute neutrophil count \>= 1,000/uL (mcL)
• TUMOR BIOPSY SEQUENCING: Platelets \>= 100,000/uL (mcL)
• TUMOR BIOPSY SEQUENCING: Total bilirubin \< 1.5 x institutional upper limit of normal
• TUMOR BIOPSY SEQUENCING: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal
• TUMOR BIOPSY SEQUENCING: Creatinine \< 1.5 x institutional upper limit of normal OR creatinine clearance \>= 60 mL/min for patients with creatinine levels \>= 1.5 x institutional upper limit of normal
• TUMOR BIOPSY SEQUENCING: The effects of these targeted agents on the developing human fetus are unknown or anticipated to cause fetal harm based on their mechanism of action; for this reason, women of childbearing potential and men must agree to use highly effective contraception prior to study entry, for the duration of study participation, and for 3 months after completion of study; because there may be a risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued while the patient is on this trial and for 30 days following last dose of study drug
• TUMOR BIOPSY SEQUENCING: Patients with history of central nervous system (CNS) metastases who have received treatment and who either have not had seizures or have been on stable doses of anti-seizure medicine and had no seizures for 4 weeks will be eligible; enzyme-inducing anticonvulsants are contraindicated
• TUMOR BIOPSY SEQUENCING: Ability to understand and the willingness to sign a written informed consent document (subjects with impaired decision-making capacity are not eligible)
• TREATMENT: Patient must have predefined targeted mutation in tumor biopsy

You may not qualify if:

• TUMOR BIOPSY SEQUENCING: Women who are pregnant or breastfeeding
• TUMOR BIOPSY SEQUENCING: Patients who are receiving any other investigational agents; patients on other trials will be eligible as long as they are no longer receiving study treatment
• TUMOR BIOPSY SEQUENCING: Patients with uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the past 6 months, invasive fungal infections, or active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e., quantifiable hepatitis B virus \[HBV\]-DNA and/or positive hepatitis B surface antigen \[HbsAg\], quantifiable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\]) are not eligible to participate; testing for hepatitis B or other infections for eligibility will be performed only if clinically indicated
• TUMOR BIOPSY SEQUENCING: Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded; subjects with Crohn's disease or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow tablets or capsules whole; tablets or capsules must not be crushed or chewed; nasogastric or gastrostomy tube (G-tube) administration is not allowed
• TUMOR BIOPSY SEQUENCING: Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic (PK) interactions
• TUMOR BIOPSY SEQUENCING: Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded; low molecular weight heparin is permitted for prophylactic or therapeutic use
• TUMOR BIOPSY SEQUENCING: Patients who have previously been treated with the combination of temozolomide plus a PARP inhibitor should not be considered eligible for a biopsy given that these patients would not be eligible for the active veliparib plus temozolomide arm
• TREATMENT: Women who are pregnant or breastfeeding
• TREATMENT: Patients who are receiving any other investigational agents; patients on other trials will be eligible as long as they are no longer receiving study treatment
• TREATMENT: Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial; patients who have a history of seizures are not eligible to receive veliparib
• TREATMENT: Patients with uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the past 6 months, invasive fungal infections, or active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e., quantifiable hepatitis B virus (HBV)-DNA and/or positive hepatitis B surface antibody (HbsAg), quantifiable hepatitis C virus (HCV)-RNA) are not eligible to participate; testing for hepatitis B or other infections for eligibility will be performed only if clinically indicated
• TREATMENT: Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded; subjects with Crohn's disease or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow tablets or capsules whole; tablets or capsules must not be crushed or chewed; nasogastric or G-tube administration is not allowed
• TREATMENT: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions
• TREATMENT: Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics (i.e., cytochrome P450, family 3, subfamily A, polypeptide 4 \[CYP450\], P-glycoprotein \[PgP\]) of any of the study drugs will be determined following review of their cases by the principal investigator (PI); patients on strong and moderate cytochrome P450 system inducers or inhibitors are ineligible; every effort would be made to switch patients off medications that are known substrates of CYP450; if it is medically important for the patient to remain on such medications, these patients can still be eligible to participate based on PI discretion
• TREATMENT: Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded; low molecular weight heparin is permitted for prophylactic or therapeutic use

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, 20892, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Lih CJ, Sims DJ, Harrington RD, Polley EC, Zhao Y, Mehaffey MG, Forbes TD, Das B, Walsh WD, Datta V, Harper KN, Bouk CH, Rubinstein LV, Simon RM, Conley BA, Chen AP, Kummar S, Doroshow JH, Williams PM. Analytical Validation and Application of a Targeted Next-Generation Sequencing Mutation-Detection Assay for Use in Treatment Assignment in the NCI-MPACT Trial. J Mol Diagn. 2016 Jan;18(1):51-67. doi: 10.1016/j.jmoldx.2015.07.006. Epub 2015 Nov 18.

  PMID: 26602013 DERIVED

MeSH Terms

Interventions

adavosertib; Carboplatin; Everolimus; Temozolomide; trametinib; veliparib

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Sirolimus; Macrolides; Lactones; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Alice P. Chen
• Organization: National Cancer Institute

chenali@mail.nih.gov

240-781-3274

Study Officials

• A P Chen

  National Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2013
• First Posted: April 9, 2013
• Study Start: January 7, 2014
• Primary Completion: June 19, 2021
• Study Completion: October 8, 2021
• Last Updated: September 29, 2023
• Results First Posted: May 10, 2022

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)