Study of Anti-HB-EGF Antibody KHK2866 in Subjects With Advanced Solid Tumors and Ovarian Cancer

NCT01279291 | Terminated Phase 1

• 1 other identifier: 2866-US-001
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 7

Brief Summary

This is a two-part, Phase 1, open-label, multicenter, dose escalation study of KHK2866 as monotherapy in patients with advanced solid tumors, and in combination with chemotherapy in subjects platinum-sensitive and platinum-resistant ovarian cancer.

Conditions

Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms; Primary Peritoneal Neoplasm

Keywords

advanced solid tumor; Ovarian cancer; Primary peritoneal cancer; Fallopian tube cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  The safety of KHK2866 will be determined by reported adverse events (AEs), changes in physical examinations, vital sign measurements, electrocardiograms (ECGs), clinical laboratory evaluations, and treatment discontinuation due to toxicity.

  at least 60 days, and up to 6 months

Secondary Outcomes (4)

• To determine the Cmax, Tmax, AUC and half life of KHK2866 when administered i.v. as monotherapy

  at least 28 days and up to 6 months

• To evaluate the changes in serum HB-EGf in participants administered KHK2866

  at least 60 days, and up to 6 months

• To screen for the development of antibodies against KHK2866 (immunogenicity).

  at least 60 days and up to 6 months

• To describe any anti-tumor activity observed when KHK2866 is administered i.v. as monotherapy, or in combination with chemotherapy.

  at least 60 days and up to 6 months

Study Arms (4)

KHK2866 as monotherapy

EXPERIMENTAL

Groups of subjects will receive a weekly infusions of KHK2866 as treatment for advanced cancer. If there no severe side effects, the dose will be increased for future subjects. A total of four groups are anticipated. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.

Biological: KHK2866

KHK2866, gemcitabine+carboplatin

EXPERIMENTAL

Open to subjects with ovarian, fallopian tube, or primary peritoneal cancer only. One group of subjects will receive one dose below the maximum tolerated dose of KHK2866 identified in Phase 1a along with gemcitabine and carboplatin. The dose of KHK2866 will be increased to the MTD for the next group if no severe side effects are noted. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.

Biological: KHK2866; Drug: Gemcitabine and Carboplatin

KHK2866, weekly paclitaxel

EXPERIMENTAL

Open to subjects with ovarian, fallopian tube, or primary peritoneal cancer only. One group of subjects will receive one dose below the maximum tolerated dose of KHK2866 identified in Phase 1a along with weekly paclitaxel (80 mg/m2). The dose of KHK2866 will be increased to the MTD for the next group if no severe side effects are noted. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.

Biological: KHK2866; Drug: paclitaxel

KHK2866, pegylated liposomal doxorubicin

EXPERIMENTAL

Open to subjects with ovarian, fallopian tube, or primary peritoneal cancer only. One group of subjects will receive one dose below the maximum tolerated dose of KHK2866 identified in Phase 1a along with monthly PLD (40 mg/m2). The dose of KHK2866 will be increased to the MTD for the next group if no severe side effects are noted. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.

Biological: KHK2866; Drug: pegylated liposomal doxorubicin

Interventions

KHK2866 BIOLOGICAL

Potentially therapeutic monoclonal antibody for the treatment of advanced cancer and ovarian cancer.

KHK2866 as monotherapy; KHK2866, gemcitabine+carboplatin; KHK2866, pegylated liposomal doxorubicin; KHK2866, weekly paclitaxel

Gemcitabine and Carboplatin DRUG

Combination chemotherapy with KHK2866 to treat advanced platinum-sensitive ovarian cancer. Gemcitabine dose 1000 mg/m2, Carboplatin dose AUC=4

Also known as: Gemzar, Paraplatin

KHK2866, gemcitabine+carboplatin

paclitaxel DRUG

Combination chemotherapy with KHK2866 to treat advanced platinum-resistant ovarian cancer. Paclitaxel will be administered weekly at a dose of 80 mg/m2.

Also known as: Taxol

KHK2866, weekly paclitaxel

pegylated liposomal doxorubicin DRUG

Combination chemotherapy with KHK2866 to treat advanced platinum-resistant ovarian cancer. PLD will be administered weekly at a dose of 40 mg/m2.

Also known as: Doxil

KHK2866, pegylated liposomal doxorubicin

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically documented, measurable or non-measurable, advanced primary or recurrent solid tumor (Phase 1a only) which is unresponsive to standard therapy or for which there is no standard therapy available.
• Histologically or cytologically documented ovarian, primary peritoneal, or fallopian tube cancer.
• The subject has objective radiographic disease progression and either unmeasurable or measurable disease during or following the last treatment regimen, or serum cancer antigen-125 (CA-125) greater than 2X the upper limit of normal (\[ULN\] \>70 U/mL
• Life expectancy \>3 months.
• Performance status \< 3 at study entry.
• Age \> 18 years.
• Normal left ventricular ejection fraction.
• Recovered from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other therapies for cancer
• Preserved hepatic, renal, and hematopoetic organ function.
• Male and female subjects must use medically accepted contraception.

You may not qualify if:

• Ovarian malignancy of low malignant potential.
• Received anti-cancer chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or investigational agents within 4 weeks prior to the first dose of KHK2866 (6 weeks for nitrosourea or mitomycin chemotherapy).
• received Mabs or had major surgery within 4 weeks of the first dose of KHK2866.
• Requires administration of a prohibited medication or treatment including: prophylactic use of erythroid and/or granulocyte colony stimulating factors; concurrent anti-cancer treatment; biologic response modifiers for any condition
• Brain metastases, leptomeningeal or primary brain neoplasm, even if treated.
• Previously untreated or uncontrolled epidural metastasis
• Cerebrovascular accident, Transient ischemic attack; symptomatic head trauma, or seizures or any kind within 6 months
• Dementia, or other disorders of mentation or difficulty speaking or difficulty with comprehension.
• Suspected impending bowel obstruction
• The subject is pregnant,or is lactating.
• Significant uncontrolled intercurrent illness
• Known HIV infection or AIDS-related illness.
• Known active hepatitis B or C or other active liver disease.
• Psychiatric illness, disability or social situation that would compromise the subject's safety, ability to provide consent, or limit his/her compliance with study requirements.
• Experienced a unmanageable hypersensitivity reactions to Mabs or other therapeutic proteins.

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead
• Kyowa Hakko Kirin Pharma, Inc.: collaborator

Study Sites (7)

Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Cedar Sinai-Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Oncology Consultants

Houston, Texas, 77030, United States

Location

Cancer Therapy and Research Center

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Sarantopoulos J, Mita MM, Birrer MJ, Cranmer LD, Campos LT, Zhang X, Bristow P, Kaito H, Strout V, Camacho LH. Phase 1 Study of Monotherapy with KHK2866, an Anti-Heparin-Binding Epidermal Growth Factor-Like Growth Factor Monoclonal Antibody, in Patients with Advanced Cancer. Target Oncol. 2016 Jun;11(3):317-27. doi: 10.1007/s11523-015-0394-5.

  PMID: 26507836 DERIVED

MeSH Terms

Conditions

Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Gemcitabine; Carboplatin; Paclitaxel; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Bruce A Silver, M.D.

  Kyowa Hakko Kirin Pharma, Inc.

  STUDY DIRECTOR

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: January 11, 2011
• First Posted: January 19, 2011
• Study Start: January 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: April 26, 2024

Record last verified: 2024-04

Locations

US (7)