MK-0646 and Gemcitabine +/- Erlotinib for Patients With Advanced Pancreatic Cancer

NCT00769483 | Completed Phase 1 Results DMC

• 2 other identifiers: 2007-0910NCI-2010-01049
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: Primary Objectives:

• Phase I: Determine the maximal tolerated dose (MTD) of MK-0646 in combination with gemcitabine or gemcitabine plus erlotinib and recommended phase II dose.
• Phase II:
• Assess progression-free survival (PFS) with a) gemcitabine plus MK-0646 b) gemcitabine plus erlotinib plus MK-0646 and c) gemcitabine plus erlotinib.
• Explore IGF1 tissue level as a predictive biomarker for MK-0646 therapy in phase II expansion cohort. Secondary Objectives:
• Assess overall response rate (ORR), treatment toxicity, and overall survival (OS) with the addition of MK-0646 to gemcitabine or gemcitabine plus erlotinib.
• Correlate PFS and OS with IGF-1, IGFBP-3 levels and the expression of p-IRS, IGF-1R, EMT biomarkers, Akt, Erk, mTOR, and PI13k in tumor cells.
• To assess the incidence of single nucleotide polymorphisms of the IgF1R pathway related genes (IGF1, IGF1R, IRS1 and IRS2). These genotypes will be correlated with the clinical endpoints of this study, including OS, ORR and PFS.

Conditions

Pancreatic Cancer; Pancreatic Adenocarcinoma

Keywords

Pancreas; Pancreatic Cancer; Advanced cancer of the pancreas; Pancreatic Adenocarcinoma; MK-0646; Gemcitabine; Gemzar; Erlotinib hydrochloride; Erlotinib; OSI-774; Tarceva

Outcome Measures

Primary Outcomes (2)

• MK-0646 Maximum Tolerable Dose

  MK-0646 10 mg/kg was declared to be the MTD in combination with gemcitabine and 5 mg/kg the MTD in combination with Gemcitabine and erlotinib

  up to 12 cycles

• Progression Free Survival

  Time interval (in months) from date of randomization until the date of first documented progression or date of death from any cause, whichever came first

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (3)

• Overall Survival

  From date of randomization until the date of death from any cause, assessed up to 100 months

• Overall Response Rate

  From start of the treatment until disease progression/recurrence; or through study completion (average of 1 year)

• Treatment Toxicity

  Through the treatment cycles

Other Outcomes (2)

• Correlation Between Tissue IGF-I Expression in Patients Treated With MK-0646 and OS

  After completing treatment

• Correlation Between Plasma IGF-I Expression in Patients Treated With MK-0646 and OS

  After completing treatment

Study Arms (5)

Phase I, Arm A

EXPERIMENTAL

MK-0646 + Gemcitabine

Drug: MK-0646; Drug: Gemcitabine

Phase I, Arm B

EXPERIMENTAL

MK-0646 + Gemcitabine + Erlotinib

Drug: MK-0646; Drug: Gemcitabine; Drug: Erlotinib

Phase II, Arm A

EXPERIMENTAL

Gemcitabine + Erlotinib

Drug: MK-0646; Drug: Gemcitabine

Phase II, Arm B

EXPERIMENTAL

MK-0646 + Gemcitabine + Erlotinib

Drug: MK-0646; Drug: Gemcitabine; Drug: Erlotinib

Phase II, Arm C

EXPERIMENTAL

Gemcitabine + Erlotinib

Drug: Gemcitabine; Drug: Erlotinib

Interventions

MK-0646 DRUG

Starting Dose Level: 5 mg/kg given intravenously over 60 minutes Days 1, 8, 15, 22 of 28 Day Cycle.

Phase I, Arm A; Phase I, Arm B; Phase II, Arm A; Phase II, Arm B

Gemcitabine DRUG

1000 mg/m\^2 given intravenously over 1-1/2 hours Days 1, 8, and 15 of each 28 Day Cycle.

Also known as: Gemzar, Gemcitabine Hydrochloride

Phase I, Arm A; Phase I, Arm B; Phase II, Arm A; Phase II, Arm B; Phase II, Arm C

Erlotinib DRUG

100 mg by mouth daily.

Also known as: OSI-774, Tarceva, Erlotinib Hydrochloride

Phase I, Arm B; Phase II, Arm B; Phase II, Arm C

Eligibility Criteria

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

You may qualify if:

• Pathologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma, AJCC stage IV
• 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 CT scan. See Section 11 for the evaluation of measurable disease. Measurable disease must be present outside a previous radiation field or if inside, it must be a new lesion.
• At least 6 months must have elapsed after completion of adjuvant therapy (if applicable).
• Age =/\>18 years.
• ECOG Performance Status 0-1 (Karnofsky =/\>60%).
• Patients must have adequate organ and marrow function as defined below: 1) leukocytes =/\>3,000 cells/mm\^3; 2) absolute neutrophil count =/\>1,500 cells/mm\^3; 4) platelets =/\>100,000 cells/mm\^3; 5) total bilirubin \<1.5mg/dl; 6) AST(SGOT)/ALT(SGPT) =/\<2.5 X institutional upper limit of normal for patients without liver metastasis, =/\< 5X institutional upper limit of normal for patients with liver metastasis; 7) creatinine - within normal institutional limits OR creatinine clearance =/\>60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Fasting blood glucose =/\<160 mg/dl, prior to study enrollment. (For higher values, blood glucose may be controlled by dietary intervention, oral hypoglycemics and/ or insulin prior to enrollment).
• Women of child-bearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use adequate contraception for the duration of study participation. Acceptable contraception is defined as double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Acceptable contraception must be used for 90 days after last dose of study drugs.
• Ability to understand and the willingness to sign a written informed consent document. Signed informed consent form must be obtained prior to initiation of study evaluations and/or activities.
• INR \<1.5 (or =/\<3 if on anticoagulation therapy)
• Both men and women and members of all races and ethnic groups are eligible for this trial.
• In phase II expansion cohort, which is primarily for predictive biomarker correlation, patients enrolled will be those with pre-existing core biopsies of primary tumor or metastatic site or must be willing to undergo a biopsy for correlative studies.

You may not qualify if:

• Prior systemic chemotherapy or biological therapy for metastatic disease
• Prior exposure to IGF-1R inhibitors.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or nursing women are excluded from this study because there is an unknown but potential risk for adverse events in infants secondary to treatment of the mother the study agents. If a pregnancy test (serum or urine) is positive, patient will be excluded.
• Patients who are known to be HIV-positive are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• No other prior malignancy is allowed except for the following: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for two years.
• Patients must not be currently enrolled in a therapeutic study for pancreatic cancer.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Abdel-Wahab R, Varadhachary GR, Bhosale PR, Wang X, Fogelman DR, Shroff RT, Overman MJ, Wolff RA, Javle M. Randomized, phase I/II study of gemcitabine plus IGF-1R antagonist (MK-0646) versus gemcitabine plus erlotinib with and without MK-0646 for advanced pancreatic adenocarcinoma. J Hematol Oncol. 2018 May 30;11(1):71. doi: 10.1186/s13045-018-0616-2.

  PMID: 29843755 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

dalotuzumab; Gemcitabine; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Milind Javle, MD/Professor, GI Medical Oncology
• Organization: UT MD Anderson Cancer Center

mjavle@mdanderson.org

713-792-2828

Study Officials

• Milind Javle, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 8, 2008
• First Posted: October 9, 2008
• Study Start: November 13, 2008
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: September 3, 2020
• Results First Posted: March 20, 2019

Record last verified: 2020-09

Locations

US (1)