Anti-PD-1 Antibody Alone or in Combination With Decitabine/Chemotherapy in Relapsed or Refractory Malignancies

Phase 1

• Conditions: Malignancies Multiple
• Interventions: Drug: Anti-PD-1 antibody; Drug: Chemotherapy; Drug: Decitabine

• Registration Number: NCT02961101
• Lead Sponsor: Han weidong

Brief Summary

The purpose of this study is to assess the feasibility, safety, and efficacy of anti-PD-1 antibody alone or in combination with low-dose decitabine in patients with relapsed or refractory malignancies, including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.

Detailed Description

Primary objective: To assess the feasibility and safety for Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy administered every 3 weeks to subjects with relapsed or refractory malignancies.

Secondary objectives: 1) To assess the antitumor activity of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy in subjects with relapsed or refractory malignancies. 2) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy. 3) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.

Exploratory objectives: 1) To analysis of potential biological parameters correlated to clinical response and toxicities. 2) To search predictive biomarkers to guide the choose of patients undergoing the treatment of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.

Safety Evaluation: Adverse events will be assessed continuously during the study and for 100 days post last treatment, and will be evaluated according to the NCI CTCAE Version 4.0.

Efficacy Evaluation: 1) Treatment response to lymphoma was defined using the International Workshop to Standardize Response Criteria for Lymphomas; 2) Treatment response to solid tumors was defined using Response Evaluation Criteria in Solid Tumors (RECIST1.1).

evaluation index: BOR; ORR; PFS and OS.

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-11-02
• Study First Submitted QC: 2016-11-08
• Study First Posted: 2016-11-10
• Primary Completion: 2019-05
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-05
• Last Update Posted: 2019-07-09
• Study Completion: 2020-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1. Subjects must have histological confirmation of relapsed or refractory malignancies,including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.

2. 12 to 75 years of age.

3. ECOG performance of less than 2.

4. Life expectancy of at least 3 months.

5. Subjects with lymphoma must have at least one measureable lesion >1 cm as defined by lymphoma response criteria; with solid tumors must have at least one measureable lesion >1 cm per RECIST1.1.

6. Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months.

7. Subjects must have adequate bone marrow, live, renal, lung and heart functions.

   1. Absolute neutrophil count greater than or equal to 1,000/μL.
   2. Platelet count greater than or equal to 70,000/µL.
   3. Serum bilirubin level less than or equal to 1.5 x upper limits of normal (ULN).
   4. Serum creatinine less than or equal to 1.5 x ULN.
   5. Alanine aminotransferase [ALT or SGPT] and aspartate aminotransferase [AST or SGOT] less than or equal to 2.5 x ULN.

Exclusion Criteria

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary and intestinal infection especially.
3. Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month .
4. Prior organ allograft.
5. Women who are pregnant or breastfeeding.
6. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anti-PD-1 antibody	Anti-PD-1 antibody	Anti-PD-1 antibody 200mg IV Q3 weeks until progression.
Anti-PD-1 antibody+chemotherapy	Anti-PD-1 antibody	Chemotherapy will be given depends on the cancer type and treatment regimen before enrollment. Chemotherapy was administrated on day1 , followed by Anti-PD-1 antibody 200mg on day2 IV Q3 weeks until progression.
Anti-PD-1 antibody+chemotherapy	Chemotherapy	Chemotherapy will be given depends on the cancer type and treatment regimen before enrollment. Chemotherapy was administrated on day1 , followed by Anti-PD-1 antibody 200mg on day2 IV Q3 weeks until progression.
Anti-PD-1 antibody+decitabine	Anti-PD-1 antibody	Decitabine will be administrated at 10mg/d on day1 to 5, followed by Anti-PD-1 antibody 200mg on day8 IV Q3 weeks until progression.
Anti-PD-1 antibody+decitabine	Decitabine	Decitabine will be administrated at 10mg/d on day1 to 5, followed by Anti-PD-1 antibody 200mg on day8 IV Q3 weeks until progression.

Primary Outcome Measures

Name	Time	Method
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.	2 years

Secondary Outcome Measures

Name	Time	Method
Overall survival	3 years
Progression free survival	3 years
Objective response by Response Evaluation Criteria in Solid Tumors (RECIST1.1).	3 years
Objective response by the International Workshop to Standardize Response Criteria for lymphomas.	3 years

Trial Locations

Locations (1)

Biotherapeutic Department of Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China