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

NCT ID: NCT01279291

Last Updated: 2024-04-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2012-11-30

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.

Detailed Description

During Phase 1a, groups of eligible patients with advanced solid tumors will receive KHK2866 as monotherapy in escalating doses. The Phase 1b portion will enroll patients with ovarian cancer who will receive KHK2866 in combination with one of three chemotherapy regimens (Arms): gemcitabine+carboplatin (platinum-sensitive, weekly paclitaxel (platinum-resistant), or pegylated liposomal doxorubicin (platinum-resistant). Escalating doses of the combination of KHK2866 and the chemotherapy regimen will given to two groups of subjects per Arm. The goal of the study is to learn about the side effects of KHK2866 alone or given in combination with chemotherapy. All subjects will receive study therapy for up to 6 cycles (up to 12 cycles for subjects assigned to PLD [Arm 3 of Phase 1b]), or until disease progression, the development of severe side effects, noncompliance or withdrawal of consent by the subject, or other removal criteria whichever comes first.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

KHK2866 as monotherapy

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.

Group Type: EXPERIMENTAL

KHK2866

Intervention Type: BIOLOGICAL

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

KHK2866, gemcitabine+carboplatin

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.

Group Type: EXPERIMENTAL

KHK2866

Intervention Type: BIOLOGICAL

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

Gemcitabine and Carboplatin

Intervention Type: DRUG

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

KHK2866, weekly paclitaxel

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.

Group Type: EXPERIMENTAL

KHK2866

Intervention Type: BIOLOGICAL

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

paclitaxel

Intervention Type: DRUG

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

KHK2866, pegylated liposomal doxorubicin

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.

Group Type: EXPERIMENTAL

KHK2866

Intervention Type: BIOLOGICAL

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

pegylated liposomal doxorubicin

Intervention Type: DRUG

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

Interventions

KHK2866

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

Intervention Type: BIOLOGICAL

Gemcitabine and Carboplatin

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

Intervention Type: DRUG

paclitaxel

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

Intervention Type: DRUG

pegylated liposomal doxorubicin

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

Intervention Type: DRUG

Other Intervention Names

Gemzar, Paraplatin; Taxol; Doxil

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• History of second primary cancer, with the exception of: a) curatively resected non-melanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 2 years.

• History of hypersensitivity or infusion reaction to any of the proposed chemotherapy arm's agents that could not be controlled with pre-medication and/or infusion rate adjustment;
• Prior treatment with KHK2866;
• History of Grade ≥ 3 non-hematologic or Grade 4 hematologic toxicity attributable to any of the proposed chemotherapy arm's agents
• For subjects proposed to receive treatment with KHK2866 plus PLD: prior total cumulative exposure to doxorubicin must be ≤ 240 mg/m2.
• Subjects with a known history of interstitial lung disease or pulmonary fibrosis. Subjects must have pulse oximetry >88% on room air at rest, and a DLco of >49% if there is no evidence of lung metastasis.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyowa Hakko Kirin Pharma, Inc.

INDUSTRY

Sponsor Role: collaborator

Kyowa Kirin Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruce A Silver, M.D.

Role: STUDY_DIRECTOR

Kyowa Hakko Kirin Pharma, Inc.

Locations

Arizona Cancer Center

Tucson, Arizona, United States

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

Cedar Sinai-Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Oncology Consultants

Houston, Texas, United States

Cancer Therapy and Research Center

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26507836 (View on PubMed)

Other Identifiers

2866-US-001

Identifier Type: -

Identifier Source: org_study_id